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We explored how a simple retrovirus, Mason-Pfizer monkey virus (M-PMV) to facilitate its replication process, utilizes DHX15, a cellular RNA helicase, typically engaged in RNA processing. Through advanced genetic engineering techniques, we showed that M-PMV recruits DHX15 by mimicking cellular mechanisms, relocating it from the nucleus to the cytoplasm to aid in viral assembly. This interaction is essential for the correct packaging of the viral genome and critical for its infectivity. Our findings offer unique insights into the mechanisms of viral manipulation of host cellular processes, highlighting a sophisticated strategy that viruses employ to leverage cellular machinery for their replication. This study adds valuable knowledge to the understanding of viral-host interactions but also suggests a common evolutionary history between cellular processes and viral mechanisms. This finding opens a unique perspective on the export mechanism of intron-retaining mRNAs in the packaging of viral genetic information and potentially develop ways to stop it. [ABSTRACT FROM AUTHOR]

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including humans, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue the replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections. [ABSTRACT FROM AUTHOR]

Introduction: Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear. Methods: We combined a single-cell sequencing approach and a wellestablished rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages. Results and discussion: Our analysis showed a decrease in the frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression in infected cells, suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages. [ABSTRACT FROM AUTHOR]

For most retroviruses, including HIV, association with the plasma membrane (PM) promotes the assembly of immature particles, which occurs simultaneously with budding and maturation. In these viruses, maturation is initiated by oligomerization of polyprotein precursors. In contrast, several retroviruses, such as Mason-Pfizer monkey virus (M-PMV), assemble in the cytoplasm into immature particles that are transported across the PM. Therefore, protease activation and specific cleavage must not occur until the pre-assembled particle interacts with the PM. This interaction is triggered by a bipartite signal consisting of a cluster of basic residues in the matrix (MA) domain of Gag polyprotein and a myristoyl moiety N-terminally attached to MA. Here, we provide evidence that myristoyl exposure from the MA core and its insertion into the PM occurs in M-PMV. By a combination of experimental methods, we show that this results in a structural change at the C-terminus of MA allowing efficient cleavage of MA from the downstream region of Gag. This suggests that, in addition to the known effect of the myristoyl switch of HIV-1 MA on the multimerization state of Gag and particle assembly, the myristoyl switch may have a regulatory role in initiating sequential cleavage of M-PMV Gag in immature particles. [ABSTRACT FROM AUTHOR]

Identifying skin diseases by using digital images of skin that are also automated, efficient, and accurate is critical for biomedical image analysis. Many researchers have developed numerous machine-learning techniques for the prediction and diagnosis of various diseases that help clinicians identify infections early and provide crucial data for virus management. In this work, we use the inherent attributes of Particle Swarm Optimization (PSO), such as exploration and exploitation, to identify images for monkey pox virus prediction and diagnosis. Alongside, monkey pox, chicken pox, small pox, cow pox, measles, tomato flu, and normal skin images were all considered in this study for monkey pox virus prediction and diagnosis. We collect photos from the International Skin Imaging Collaboration (ISIC) for analysis and experimentation purposes. Finally, we compare the proposed model Particle Swarm Optimization- Monkey pox Virus (PSOMPX) for monkey pox virus identification with four distinct pre-trained deep learning models (e.g., VGG16, ResNet50, InceptionV3, and Ensemble). Then we use four performance evaluation metrics—accuracy, precision, recall, and F1 score—to evaluate the model and analyze the outcomes of experiments. The experimental results obtained through the PSOMPX model significantly outperform other models due to its numerous traits. [ABSTRACT FROM AUTHOR]

Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic (forest) cycles involving monkeys and canopy-living Aedes mosquitoes. Both viruses spilled over into human transmission and were translocated to the Americas, opening a path for spillback into Neotropical sylvatic cycles. Studies of the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. We infected a native, Asian host species (cynomolgus macaque) and a novel, American host species (squirrel monkey) with sylvatic strains of DENV-2 or ZIKV via mosquito bite. We then monitored aspects of viral replication (viremia), innate and adaptive immune response (natural killer (NK) cells and neutralizing antibodies, respectively), and transmission to mosquitoes. In both hosts, ZIKV reached high titers that translated into high transmission to mosquitoes; in contrast DENV-2 replicated to low levels and, unexpectedly, transmission occurred only when serum viremia was below or near the limit of detection. Our data reveal evidence of an immunologically-mediated trade-off between duration and magnitude of virus replication, as higher peak ZIKV titers are associated with shorter durations of viremia, and higher NK cell levels are associated with lower peak ZIKV titers and lower anti-DENV-2 antibody levels. Furthermore, patterns of transmission of each virus from a Neotropical monkey suggest that ZIKV has greater potential than DENV-2 to establish a sylvatic transmission cycle in the Americas. Hanley et al show that transmission of dengue and Zika virus from Old and New World monkeys is shaped by an immunologically-mediated trade-off between magnitude and duration of replication. Patterns of Zika transmission suggests high risk of spillback into neotropical monkeys. [ABSTRACT FROM AUTHOR]

Cancer in dogs has increased in recent years and is a leading cause of death. We have developed a retroviral replicating vector (RRV) that specifically targets cancer cells for infection and replication. RRV carrying a suicide gene induced synchronized killing of cancer cells when administered with a prodrug after infection. In this study, we evaluated two distinct RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) in canine tumor models both in vitro and in vivo. Despite low infection rates in normal canine cells, both RRVs efficiently infected and replicated within all the canine tumor cells tested. The efficient intratumoral spread of the RRVs after their intratumoral injection was also demonstrated in nude mouse models of subcutaneous canine tumor xenografts. When both RRVs encoded a yeast cytosine deaminase suicide gene, which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil, they caused tumor-cell-specific 5-FC-induced killing of the canine tumor cells in vitro. Furthermore, in the AZACF- and AZACH-cell subcutaneous tumor xenograft models, both RRVs exerted significant antitumor effects. These results suggest that RRV-mediated suicide gene therapy is a novel therapeutic approach to canine cancers. [ABSTRACT FROM AUTHOR]

A zoonotic orthopoxvirus called human monkeypox has symptoms that resemble smallpox. When people come into contact with diseased animals, they may unintentionally contract monkeypox. According to reports, the virus can also spread through close physical contact, such as skin-to-skin contact or sexual contact, respiratory droplets, and by household items like towels and blankets. There are numerous medical countermeasures on hand for orthopoxviruses like monkeypox. Monkeypox, which originated in western and central Africa, has lately been found in a integer of nations, counting Spain, Canada, Australia, and the United Arab Emirates. Despite its extremely low incidence rate, it nonetheless poses a serious concern that needs to be addressed as soon as possible because of the strong likelihood that it will spread to many other nations. Outside of endemic areas, the danger of monkeypox transmission in medical settings is not well known. One recorded instance of transmission was found after a quick assessment of the literature from 2000 to 2022, which also included cases outside of areas where monkeypox is endemic. It is unusual for monkeypox to recur in non-endemic nations. It is a zoonosis that can extend from animal to human and from human to human, and it has clinical characteristics comparable to smallpox. The latest outbreaks may be attributed to lowered resistance to the orthopoxviruses, movement of people from widespread to non-endemic areas, hereditary alterations in the viral genome, and diminished observation. Transmission and pathogenicity could be avoided with the use of a multifaceted strategy that includes health education, monitoring human mobility, the development of diagnostic tools, and an efficient vaccination. [ABSTRACT FROM AUTHOR]

Germline colonization by retroviruses results in the formation of endogenous retroviruses (ERVs). Most colonization’s occurred millions of years ago. However, in the Australo-Papuan region (Australia and New Guinea), several recent germline colonization events have been discovered. The Wallace Line separates much of Southeast Asia from the Australo-Papuan region restricting faunal and pathogen dispersion. West of the Wallace Line, gibbon ape leukemia viruses (GALVs) have been isolated from captive gibbons. Two microbat species from China appear to have been infected naturally. East of Wallace’s Line, the woolly monkey virus (a GALV) and the closely related koala retrovirus (KoRV) have been detected in eutherians and marsupials in the Australo-Papuan region, often vertically transmitted. The detected vertically transmitted GALV-like viruses in Australo-Papuan fauna compared to sporadic horizontal transmission in Southeast Asia and China suggest the GALV-KoRV clade originates in the former region and further models of early-stage genome colonization may be found. We screened 278 samples, seven bat and one rodent family endemic to the Australo-Papuan region and bat and rodent species found on both sides of the Wallace Line. We identified two rodents (Melomys) from Australia and Papua New Guinea and no bat species harboring GALV-like retroviruses. Melomys leucogaster from New Guinea harbored a genomically complete replication-competent retrovirus with a shared integration site among individuals. The integration was only present in some individuals of the species indicating this retrovirus is at the earliest stages of germline colonization of the Melomys genome, providing a new small wild mammal model of early-stage genome colonization. [ABSTRACT FROM AUTHOR]

Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aβ42/Aβ40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aβ42/Aβ40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aβ42/Aβ40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease. [ABSTRACT FROM AUTHOR]

The administration of vaccines using a combination approach ensures better coverage and reduces the number of injections and cost. The present study assessed liposome-complexed DNA-corresponding proteins of hepatitis E and B viruses (HEV and HBV) as combined vaccine candidates in rhesus monkeys. The HEV and HBV components consisted of 450 bps, neutralizing the epitope/s (NE) region, and 685 bps small (S) envelope gene-corresponding proteins, respectively. Three groups (n = 2 monkeys/group) were intramuscularly immunized with a total of three doses of NE Protein (Lipo-NE-P), NE DNA + Protein (Lipo-NE-DP), and each of NE and S DNA + Protein (Lipo-NES-DP), respectively, given one month apart. All immunized monkeys were challenged with 10,000 fifty percent monkey infectious dose of homologous HEV strain. Post-immunization anti-HEV antibody levels in monkeys were 59.4 and 148.4 IU/mL (Lipo-NE-P), 177.0 and 240.8 IU/mL (Lipo-NE-DP), and 240.7 and 164.9 IU/mL (Lipo-NES-DP). Anti-HBV antibody levels in Lipo-NES-DP immunized monkeys were 58,786 and 6213 mIU/mL. None of the challenged monkeys showed viremia and elevation in serum alanine amino transferase levels. Monkeys immunized with Lipo-NE-DP and Lipo-NES-DP exhibited a sterilizing immunity, indicating complete protection, whereas monkeys immunized with Lipo-NE-P showed limited viral replication. In conclusion, the liposome-complexed DNA-corresponding proteins of HEV and HBV induced protective humoral immune responses to both components in monkeys and are worth exploring further. [ABSTRACT FROM AUTHOR]

Will a warmer world be a sicker world? What is it about the New England landscape that supports the proliferation of Lyme disease? How are local wildlife trade and global species invasions contributors to emerging diseases such as the 2003 outbreak of monkey pox virus in the midwestern United States? Undergraduate students explore these and related questions in BIOL 1455 Planetary Health: global environmental change and emerging infectious disease—a new online asynchronous course at Brown University. Planetary health is gaining traction in the curricula of institutions of higher learning and online asynchronous courses offer the promise of scaling up to make grand challenges education accessible to many. In our new course, we assessed student learning outcomes (LOs) and sentiment towards the health of humans and the planet using a mixed-methods approach. Students demonstrated competency in each of the LOs after course completion as measured in a pre–post assessment scored with a standardized rubric. Student sentiment was analyzed with an immersion–crystallization qualitative analysis to elucidate themes in responses to the assessments. Many themes on the pre-assessment focused on barriers and problems associated with the health of humans and the planet, while themes on the post-assessment centered on more solutions-based thinking. Collectively, these findings indicate that this online asynchronous course successfully educated students about the myriad challenges facing human and planetary health, broadened knowledge of environmental changes (beyond climate change) that impact health, formalized understanding of now common terms such as "emerging infectious diseases", and bolstered hope by offering solutions and peer community (even when virtual). Future efforts to integrate planetary health into higher education should focus on broadly accessible and scalable courses, full programs of study (i.e., majors/scholarly concentrations), and extension into institutional programs focused on ensuring equity and wellness for all. [ABSTRACT FROM AUTHOR]

The article informs about the origin of HTLV-1, the first human retrovirus, which originated from simian T-lymphotropic virus in Central and Western Sub-Saharan Africa thousands of years ago, spreading to Latin America through migrations and colonial trade routes. Topic include four major areas in Latin America with high HTLV-1 prevalence: the Caribbean basin, Brazil, Peru, and along the Andes mountains, each influenced by distinct historical events such as ancient migrations and colonialism.

BACKGROUND: The biological characteristics of animal osteoblast models widely used at this stage are quite different from those of human cells. The primary human osteoblasts isolated and cultured are difficultly purified, and the culture generations are limited. Osteosarcoma cells have the risk of abnormal growth, which cannot fully meet the research requirements. In 1995, Harris transfected human fetal limb cells with simian vacuolating virus 40, and screened a group of immortalized human osteoblast cell line hFOB1.19 that differentiated into earlier osteogenic progenitor cells. OBJECTIVE: To review the basic characteristics, culture methods and application of hFOB1.19 as a cell model of bone tissue engineering materials. METHODS: Relevant literature published from 1995 to May 2022 was retrieved in CNKI, WanFang, SinoMed, PubMed, Web of Science, Medicine, and Cochrane Library databases. The keywords were “hFOB1. 19, human osteoblast cell line, immortalized cells, monkey vacuolating virus 40, bone tissue engineering, bone substitute materials, biomaterials research” in Chinese and English, respectively. Finally, 73 papers were screened for review. RESULTS AND CONCLUSION: hFOB1.19 is highly similar to osteoblasts in vivo in terms of morphology, phenotype, karyotype, biological characteristics, and differentiation potential, which has the ability of rapid and stable growth. hFOB1.19 has been widely used in cell adhesion, proliferation, differentiation, mineralization, gene expression, and protein synthesis to test the biocompatibility and osteogenic properties of bone tissue engineering materials. hFOB1.19 can make up for the shortcomings of different animal cell sources, abnormal proliferation of osteosarcoma cells, difficult separation of primary osteoblasts, and few passages. It has stable performance and good proliferation in bone tissue engineering experiments. However, due to the special culture conditions, limitation of cell passage number and biosafety, it is not widely used in the field of bone tissue engineering materials. At present, the development of bone tissue engineering materials is fast, but there is a lack of a systematic and comprehensive research system and popularization of a unified research standard in the development process. This article summarizes the application of hFOB1.19 in different studies to provide researchers with guidance for method selection and improve relevant standards. [ABSTRACT FROM AUTHOR]

Pathogen surveillance for great ape health monitoring has typically been performed on non-invasive samples, primarily feces, in wild apes and blood in sanctuary-housed apes. However, many important primate pathogens, including known zoonoses, are shed in saliva and transmitted via oral fluids. Using metagenomic methods, we identified viruses in saliva samples from 46 wild-born, sanctuary-housed chimpanzees at two African sanctuaries in Republic of Congo and Uganda. In total, we identified 20 viruses. All but one, an unclassified CRESS DNA virus, are classified in five families: Circoviridae, Herpesviridae, Papillomaviridae, Picobirnaviridae, and Retroviridae. Overall, viral prevalence ranged from 4.2% to 87.5%. Many of these viruses are ubiquitous in primates and known to replicate in the oral cavity (simian foamy viruses, Retroviridae; a cytomegalovirus and lymphocryptovirus; Herpesviridae; and alpha and gamma papillomaviruses, Papillomaviridae). None of the viruses identified have been shown to cause disease in chimpanzees or, to our knowledge, in humans. These data suggest that the risk of zoonotic viral disease from chimpanzee oral fluids in sanctuaries may be lower than commonly assumed. [ABSTRACT FROM AUTHOR]

Japanese encephalitis virus (JEV) is a member of the Flaviviridae family and one of Asia's most common causes of encephalitis. JEV is a zoonotic virus that is transmitted to humans through the bite of infected mosquitoes of the Culex species. While humans are dead-end hosts for the virus, domestic animals such as pigs and birds are amplification hosts. Although JEV naturally infected monkeys have been reported in Asia, the role of non-human primates (NHPs) in the JEV transmission cycle has not been intensively investigated. In this study, we demonstrated neutralizing antibodies against JEV in NHPs (Macaca fascicularis) and humans living in proximity in two provinces located in western and eastern Thailand by using Plaque Reduction Neutralization Test (PRNT). We found a 14.7% and 5.6% seropositive rate in monkeys and 43.7% and 45.2% seropositive rate in humans living in west and east Thailand, respectively. This study observed a higher seropositivity rate in the older age group in humans. The presence of JEV neutralizing antibodies in NHPs that live in proximity to humans shows the occurrence of natural JEV infection, suggesting the endemic transmission of this virus in NHPs. According to the One Health concept, regular serological studies should be conducted especially at the animal–human interface. [ABSTRACT FROM AUTHOR]

Infection with viruses of animal origin pose a significant threat to human populations. Simian foamy viruses (SFVs) are frequently transmitted to humans, in which they establish a life-long infection, with the persistence of replication-competent virus. However, zoonotic SFVs do not induce severe disease nor are they transmitted between humans. Thus, SFVs represent a model of zoonotic retroviruses that lead to a chronic infection successfully controlled by the human immune system. We previously showed that infected humans develop potent neutralizing antibodies (nAbs). Within the viral envelope (Env), the surface protein (SU) carries a variable region that defines two genotypes, overlaps with the receptor binding domain (RBD), and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs present in plasma samples from SFV-infected individuals living in Central Africa. Neutralization assays were carried out in the presence of recombinant SU that compete with SU at the surface of viral vector particles. We defined the regions targeted by the nAbs using mutant SU proteins modified at the glycosylation sites, RBD functional subregions, and genotype-specific sequences that present properties of B-cell epitopes. We observed that nAbs target conformational epitopes. We identified three major epitopic regions: the loops at the apex of the RBD, which likely mediate interactions between Env protomers to form Env trimers, a loop located in the vicinity of the heparan binding site, and a region proximal to the highly conserved glycosylation site N8. We provide information on how nAbs specific for each of the two viral genotypes target different epitopes. Two common immune escape mechanisms, sequence variation and glycan shielding, were not observed. We propose a model according to which the neutralization mechanisms rely on the nAbs to block the Env conformational change and/or interfere with binding to susceptible cells. As the SFV RBD is structurally different from known retroviral RBDs, our data provide fundamental knowledge on the structural basis for the inhibition of viruses by nAbs. Trial registration: The study was registered at www.clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03225794/. Author summary: Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. Simian foamy viruses (SFVs) can be transmitted to humans, in whom they establish persistent infection, as have the simian viruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus type 1 (HTLV-1). Such cross-species transmission of SFV is ongoing in many parts of the world where humans have contact with nonhuman primates. We previously showed high titers of neutralizing antibodies (nAbs) in the plasma of most SFV-infected individuals. These antiviral antibodies can inhibit cell-free virus entry. Here, we have identified three sites on viral envelope that are targeted by nAbs. We propose that nAbs block the Env conformational change and/or interfere with binding to susceptible cells. We did not observe escape mechanism common in other retroviruses. Our data support the capacity of nAbs to prevent SFV spread. [ABSTRACT FROM AUTHOR]

Background: Smallpox-like symptoms are seen in the viral zoonotic illness known as monkeypox. In the current outbreaks being reported, the World Health Organization (WHO) claims that this is the first instance of chains of transmission being documented in Europe without known epidemiological connections to West or Central Africa. On August 7, 2022, the WHO reported a total of 27,815 confirmed cases in over 89 countries, with the majority of those affected experiencing monkeypox for the first time. The objective of this article is to provide a succinct overview of the monkey pox, its transmission mechanisms, and available preventative methods in adolescents. Materials and Methods: Several databases, including WHO guidelines, PubMed, Bentham Science, and Elsevier, were used to compile the data for the article following a thorough analysis of the various research findings connected to monkey pox infection, pathogenesis, and available treatments. Results: Monkeypox is a zoonotic orthopoxvirus that causes disease in humans similar to smallpox. Complications are more likely in children and the immunocompromised. Treatment is largely symptomatic. The first-line treatment for monkeypox, including in kids and teenagers, is tecovirimat. Conclusion: We came to the conclusion from this review that adolescents and adults both transmit the monkey pox virus. The most common sign of monkeypox in kids and teens is a rash that starts out as maculopapular lesions and turns into vesicles, pustules, and then scabs, just like diseases in adults. Children and adolescents who have been exposed to individuals with suspected or confirmed monkeypox may benefit from Post-Exposure Prophylaxis (PEP) with vaccination, immune globulin, or antiviral medicine. [ABSTRACT FROM AUTHOR]

Transmissions of simian viruses to humans has originated the different groups of HIV-1. We recently identified a functional motif (CLA), in the C-terminal domain of the integrase, essential for integration in HIV-1 group M. Here, we found that the motif is instead dispensable in group O isolates, because of the presence, in the N-terminal domain of HIV-1 O of a specific sequence, Q7G27P41H44, that we define as the NOG motif. Alterations of reverse transcription and of 3' processing observed by mutating the CLA motif of IN M are fully rescued to wt levels by inserting the sequence of the NOG motif in the N-ter of the protein. These results indicate that the two motifs (CLA and NOG) functionally complement each other and a working model accounting for these observations is proposed. The establishment of these two alternative motifs seems to be due to the different phylogenetic origin and history of these two groups. Indeed, the NOG motif is already present in the ancestor of group O (SIVgor) while it is absent from SIVcpzPtt, the ancestor of group M. The CLA motif, instead, seems to have emerged after SIVcpzPtt has been transferred to humans, since no conservation is found at the same positions in these simian viruses. These results show the existence of two-group specific motifs in HIV-1 M and O integrases. In each group, only one of the motifs is functional, potentially leading the other motif to diverge from its original function and, in an evolutionary perspective, assist other functions of the protein, further increasing HIV genetic diversity. Author summary: HIV-1 establishes a permanent infection by integrating its genome in the one of the host cell. This key step is achieved by the viral integrase (IN), which is composed of three domains: N-terminal (NTD), catalytic core (CCD), and C-terminal (CTD). We recently reported, in the CTD, the existence of a functional motif (CLA) that is essential for integration in HIV-1 group M. Here we show that in HIV-1 group O, the function exerted by the integrase M CLA motif is instead ensured by another motif (NOG), located in the NTD of the protein. We show that these two motifs can functionally complement each other by acting on the same steps of the viral cycle, highlighting for the first time such an important functional duality between HIV-1 integrases. We also show that, while the NOG motif in HIV-1 O was likely inherited from its simian ancestor (SIVgor), the CLA motif seems to have emerged in the human host, probably in the process of adaptation to the new host of the simian virus on its way to become HIV-1 M. Such a requirement did not seem to have existed for HIV-1 O, possibly because of the presence of the NOG motif. [ABSTRACT FROM AUTHOR]

Human mpox is an emerging epidemic in the world. The monkey pox virus (MPXV) belongs to the same family of zoonotic Orthopoxviridae as that of the smallpox virus and exhibits similar clinical symptomology. Information regarding its diagnostics, disease epidemiology, surveillance, preventive methods, and treatment strategies are being collated with time. The purpose of this review is to trace the recent events in the scientific platform that have defined new preventive and treatment strategies against mpox. A methodological approach has been used to gather data from the latest literature to comprehensively overview the emerging treatment options. The results portion will cover details regarding the prevention of mpox. It will also shed light on a brief description of contemporary vaccines and antiviral agents that have been evaluated for their treatment potential since the emergence of the mpox threat. These treatment options are setting the pace for controlling the widespread monkeypox infection. However, the limitations attached to these treatment strategies need to be tackled quickly to increase their efficacy so that they can be deployed on a large scale for the prevention of this epidemic becoming another pandemic in this decade. [ABSTRACT FROM AUTHOR]

Introduction: Rhesus macaques are natural hosts to multiple viruses including rhesus cytomegalovirus (RhCMV), rhesus rhadinovirus (RRV), and Simian Foamy Virus (SFV). While viral infections are ubiquitous, viral transmissions to uninfected animals are incompletely defined. Management procedures of macaque colonies include cohorts that are Specific Pathogen Free (SPF). Greater understanding of viral transmission would augment SPF protocols. Moreover, vaccine/challenge studies of human viruses would be enhanced by leveraging transmission of macaque viruses to recapitulate expected challenges of human vaccine trials. Materials and Methods: This study characterizes viral transmissions to uninfected animals following inadvertent introduction of RhCMV/RRV/SFV‐infected adults to a cohort of uninfected juveniles. Following co‐housing with virus‐positive adults, juveniles were serially evaluated for viral infection. Results: Horizontal viral transmission was rapid and absolute, reaching 100% penetrance between 19 and 78 weeks. Conclusions: This study provides insights into viral natural histories with implications for colony management and modeling vaccine‐mediated immune protection studies. [ABSTRACT FROM AUTHOR]

The world is about to see the rapid spread of the Zika virus. Zika in South Africa's woodland is not there. The febrile sentinel rhesus monkey serves as a virus's source of identification. The most common carrier is the mosquito. Currently, ZIKV does not have a particular, practicable treatment. Sofosbuvir, boceprevir, acyclovir, atazanavir, and other antiviral synthetic medicines are available, but, at this time, it is unlikely that they will be effective in treating ZIKV. Some significant negative consequences are also produced. This study's overarching issue is that we must solve. In the Indian medical system, the plant Aegel marmelos was widely utilized. The field is quickly evolving. The plant phytoconstituents of Aegel marmelos are predicted to be protective against the Zika virus using a molecular docking study technique. The novel possible active principle to inhibit the Zika virus expansion using the molecular modelling program Schrodinger Maestro 12.7. Also performing ADME screening is the Qikprop tool. The Aegel marmelos plants yielded 60 phytoconstituents for our collection. Comparing the Rutin to other phytoconstituents, the Rutin exhibit a high docking score. Rutin adjusted all drug-likeness characteristics to fit the requirements. Rutin has a higher docking score (-11.471 kcal/mol) than the standard medicine sofosbuvir (-5.5 kcal/mol). The findings indicate that could be advantageous as the leading pharmacological candidate for Zika virus inhibitors. [ABSTRACT FROM AUTHOR]

• Human monkey pox virus (hMPXV) in this outbreak mostly affects males and those who self-identify as gay, bisexual, or men who have sex with men. • Lymphadenopathy was associated with a higher likelihood of a positive result. • Rash in hMPXV was more likely present in the genital or buttocks/perianal region. • HIV positivity was not associated with an increased likelihood of positive hMPXV. • Blood tests were not useful discriminators; rapid diagnostics are urgently needed. Since May 2022, cases of human monkeypox virus (hMPXV) with human-to-human cross-transmission have significantly increased in nonendemic countries. Our aim was to characterize diagnostic features of patients with confirmed and possible monkeypox to guide future risk stratification and to describe a virtual care model. We performed a retrospective case-control study of 140 patients assessed and screened for suspected monkeypox; on hMPXV polymerase chain reaction testing, 70 were confirmed positive, and 70 were negative. Data were compared to generate odds ratios of demographic and clinical features. Patients who tested positive were predominantly cis-male (99%) and self-identified as gay, bisexual, and other men who have sex with men (94%). Lymphadenopathy at presentation was associated with a higher likelihood of a positive result (odds ratio [OR] 7.69 [95% confidence interval (CI) 3.58, 16.51]). Patients who tested positive were more likely to have a rash affecting the genital (OR 5.38 [95% CI 2.57, 11.23]) or buttocks/perianal region (OR 3.79 [1.70, 8.45]) than negative controls. A total of 79% of patients were engaged with a virtual ward follow-up. These data can inform a risk-based approach to the management of suspected monkeypox in gay, bisexual, and other men who have sex with men populations. Lymphadenopathy at presentation and the location of the rash were more associated with a positive hMPXV result. Health authorities can consider a virtual ward approach in the hMPHXV outbreak. [ABSTRACT FROM AUTHOR]

In this research work, we offer an epidemic model for monkeypox virus infection with the help of non-integer derivative as well as classical ones. The model takes into account every potential connection that can aid in the spread of infection among the people. We look into the model's endemic equilibrium, disease-free equilibrium, and reproduction number ℛ 0 . In addition to this, we concentrated on the qualitative analysis and dynamic behavior of the monkeypox virus. Through fixed point theorem, Banach's and Schaefer's are applied to study the existence and uniqueness of the solution of the suggested system of the monkeypox virus infection. We provide the necessary criteria for the recommended fractional system's Ulam–Hyers stability. Furthermore, a numerical approach is used to study the solution routes and emphasize how the parameters affect the dynamics of the monkey pox virus. The most crucial features of the dynamics of the monkeypox virus are noticed and suggested to decision-makers. [ABSTRACT FROM AUTHOR]

The world has been facing a back-to-back hit to life after widespread of viruses since the time of COVID-19. The pandemic had a devastating effect and created history in mankind, but that was not enough for the time. The viruses are been known to be the deadliest microbes by virtue of their ability to reside as inactive for long time and become active again along with new variants when the conditions are favourable. One such noted spread out of virus has been that of Monkeypox Virus in humans. A zoonotic orthopoxvirus that can infect humans, the monkeypox virus (MPV) can cause disease with varied morbidity and death in humans. It has been demonstrated that members of the Orthopoxvirus genus decrease antiviral cell defences, take advantage of host cell machinery, and postpone infection-induced cell death. The name Monkeypox was after its first observation in Macaque monkey but the virus's origin has been linked to a number of rodents and small mammals. The virus was endemic to Africa and is closely related to notorious variola (smallpox) virus. They both affect people with a febrile rash sickness that is similar to smallpox but has less severity. Monkeypox can spread from person to person and it is frequently related to breathing droplets or direct contact with mucocutaneous lesions of an affected person. There is now no cure available for those who are affected, yet supporting therapies can be used to help people with their symptoms. To better comprehend and prevent human infections, additional study is required on the epidemiology, ecology, mutations and biology of the new virus strains in endemic locations. [ABSTRACT FROM AUTHOR]

Viral vectors derived from human immunodeficiency virus type 1 (HIV-1) mediate efficient stable gene transduction. Consequently, these vectors are utilized in gene therapeutic approaches. We here aimed for improving HIV-1 pseudotype vector formation using envelope proteins (Env) of ecotropic murine leukemia virus (MLV) suffering deletions of the R-peptide and further amino acid substitutions in their cytoplasmatic domains. All examined Env variants revealed cell-surface expression and showed elevated fusogenicity as compared to wildtype (eMLV-wt) Env but failed to efficiently pseudotype MLV particles. However, two variants generated ecotropic HIV-1 pseudotype vectors with superior infectivity. Most importantly, pseudotyping with the variant eMLV-GaLVΔR encompassing the R-peptide-deleted cytoplasmic domain of the gibbon ape leukemia virus Env yielded titers three-fold higher than HIV(eMLV-wt) vectors. We anticipate that superior ecotropic HIV(eMLV-GaLVΔR) pseudotype vectors will be of utility in preclinical gene therapy studies aiming at the genetic modification of primary murine cells. • Truncated envelope proteins of ecotropic MLV lacking the R-peptide fail to efficiently incorporate into MLV derived vector particles. • Two R-peptide-deleted Env variants are incorporated into HIV-1 vector particles. • The Env variant encompassing the wt GaLV cytoplasmic domain but no R-peptide elevates HIV-1 vector by more than three-fold. [ABSTRACT FROM AUTHOR]

We evaluated the use of the Product Enhanced Reverse Transcriptase (PERT) assay as a means of detecting virus in retroviral vectors products pseudotyped with Gibbon Ape Leukemia Virus (GALV) and Vesicular Stomatitis Virus G (VSVG) envelopes. PERT provides greater standardization than the S+/L- assay which has been used extensively in virus detection. A challenge is that PERT will also detect residual retroviral vectors as vector particles contain reverse transcriptase. Vector products were cultured for 3 weeks on HEK293 cells to amplify any potential virus. In addition, vector supernatant and end-of-production cells were spiked with GALV to evaluate for inhibition by the test article. Results of PERT and the S+/L- assay were compared. PERT and S+/L- assays were both effective in detecting virus. Vector supernatants were negative at the end of 3 weeks of culture by PERT for both GAVL and VSVG pseudotyped vector. In contrast, end-of-production cells were positive by PERT due to persistent vector producing cells. A one-week culture of cell-free media obtained at the 3 weeks timepoint allowed distinction of virus-free test articles from those with virus. The PERT assay is suitable for detecting replication competent retrovirus in vector products pseudotyped with GALV and VSVG envelopes. • Retroviral vectors have been associated with cancers. • Ensuring retroviral vectors are free of replication competent viruses is required by regulatory bodies. • Distinguishing retroviruses from retroviral vectors requires biologic assays. • The PERT assay has similar sensitivity and fosters standardization in detecting replication competent retroviruses. [ABSTRACT FROM AUTHOR]

Signal-dependent transport into and out of the nucleus mediated by members of the importin (IMP) superfamily of nuclear transporters is critical to the eukaryotic function and a point of therapeutic intervention with the potential to limit disease progression and pathogenic outcomes. Although the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii both retain unique IMPα genes that are essential, a detailed analysis of their properties has not been performed. As a first step to validate apicomplexan IMPα as a target, we set out to compare the properties of P. falciparum and T. gondii IMPα (PfIMPα and TgIMPα, respectively) to those of mammalian IMPα, as exemplified by Mus musculus IMPα (MmIMPα). Close similarities were evident, with all three showing high-affinity binding to modular nuclear localisation signals (NLSs) from apicomplexans as well as Simian virus SV40 large tumour antigen (T-ag). PfIMPα and TgIMPα were also capable of binding to mammalian IMPβ1 (MmIMPβ1) with high affinity; strikingly, NLS binding by PfIMPα and TgIMPα could be inhibited by the mammalian IMPα targeting small molecules ivermectin and GW5074 through direct binding to PfIMPα and TgIMPα to perturb the α-helical structure. Importantly, GW5074 could be shown for the first time to resemble ivermectin in being able to limit growth of P. falciparum. The results confirm apicomplexan IMPα as a viable target for the development of therapeutics, with agents targeting it worthy of further consideration as an antimalarial. [ABSTRACT FROM AUTHOR]

Monkey pox is an infectious viral disease which spread from animals to humans. This virus is a new concern, as recently the identification of emerging cases of monkey pox virus other than African Continent in May 2022.It showed its spread in other parts of world because of international tourism and exchange of certain animals. Hence it is important to evaluate and discuss the management of monkeypox infections in humans to prevent the spread of the disease. The objective of this review is discuss the spread of monkey pox disease world-wide, study its symptoms for prompt identification of the disease with the aim to abolish all possible modes of transmission to protect public health and to prevent the possibility of spread of another pandemic, after COVID-19. [ABSTRACT FROM AUTHOR]

Equine foamy virus (EFVeca) is a foamy virus of non-primate origin and among the least-studied members of this retroviral subfamily. By sequence comparison, EFVeca shows the highest similarity to bovine foamy virus. In contrast to simian, bovine or feline foamy viruses, knowledge about the epidemiology of EFVeca is still limited. Since preliminary studies suggested EFVeca infections among horses in Poland, we aimed to expand the diagnostics of EFVeca infections by developing specific diagnostic tools and apply them to investigate its prevalence. An ELISA test based on recombinant EFVeca Gag protein was developed for serological investigation, while semi-nested PCR for the detection of EFVeca DNA was established. 248 DNA and serum samples from purebred horses, livestock and saddle horses, Hucul horses and semi-feral Polish primitive horses were analyzed in this study. ELISA was standardized, and cut off value, sensitivity and specificity of the test were calculated using Receiver Operating Characteristic and Bayesian estimation. Based on the calculated cut off, 135 horses were seropositive to EFVeca Gag protein, while EFVeca proviral DNA was detected in 85 animals. The rate of infected individuals varied among the horse groups studied; this is the first report confirming the existence of EFVeca infections in horses from Poland using virus-specific tools. [ABSTRACT FROM AUTHOR]

Primary simian varicella virus (SVV) infection and reactivation in nonhuman primates is a valuable animal model in the study of varicella zoster virus disease [varicella (chickenpox) and herpes zoster (shingles)]. To understand SVV pathogenesis in skin, we inoculated 10 rhesus macaques with SVV, resulting in varicella rash. After the establishment of latency, eight of the monkeys were immunosuppressed using tacrolimus with or without irradiation and prednisone and two monkeys were not immunosuppressed. Zoster rash developed in all immunosuppressed monkeys and in one non-immunosuppressed monkey. Five monkeys had recurrent zoster. During varicella and zoster, SVV DNA in skin scrapings ranged from 50 to 107 copies/100 ng of total DNA and 2–127 copies/100 ng of total DNA, respectively. Detection of SVV DNA in blood during varicella was more frequent and abundant compared to that of zoster. During varicella and zoster, SVV antigens colocalized with neurons expressing β-III tubulin in epidermis, hair follicles, and sweat glands, suggesting axonal transport of the virus. Together, we have demonstrated that both SVV DNA and antigens can be detected in skin lesions during varicella and zoster, providing the basis for further studies on SVV skin pathogenesis, including immune responses and mechanisms of peripheral spread. [ABSTRACT FROM AUTHOR]

A Tn7-transposition approach was utilized for site-specific insertion of foreign genes into the genome of simian varicella virus (SVV), the causative agent of simian varicella in nonhuman primates. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) nucleocapsid (N) gene and receptor binding domain (RBD) of the spike gene were inserted into the ORF 14 region of the SVV genome cloned into a bacterial artificial chromosome and then transfected into Vero cells to generate the infectious recombinant SVV (rSVV). The rSVV replicated efficiently in infected Vero cells and expressed the N and RBD antigens as indicated by immunoblot and immunofluorescence assays. Tn7-mediated transposition provides a rapid and efficient method for constructing rSVVs which may be evaluated as live-attenuated vaccines. • A TN7-mediated transposon method was used to insert foreign genes into the simian varicella virus (SVV) genome. • The SARS-CoV-2 nucleocapsid (N) and receptor binding domain (RBD) DNA sequences were inserted into the ORF 14 the SVV genome. • Recombinant SVV expressed the SARS-CoV-2 N and RBD antigens in infected Vero cells. • Recombinant SVV expressing the SARS-CoV-2 N and RBD replicated as efficiently as wild-type SVV. [ABSTRACT FROM AUTHOR]

Zoonotic simian foamy viruses (SFV) establish lifelong infection in their human hosts. Despite repeated transmission of SFV from nonhuman primates to humans, neither transmission between human hosts nor severe clinical manifestations have been reported. We aim to study the immune responses elicited by chronic infection with this retrovirus and previously reported that SFV-infected individuals generate potent neutralizing antibodies that block cell infection by viral particles. Here, we assessed whether human plasma antibodies block SFV cell-to-cell transmission and present the first description of cell-to-cell spreading of zoonotic gorilla SFV. We set-up a microtitration assay to quantify the ability of plasma samples from 20 Central African individuals infected with gorilla SFV and 9 uninfected controls to block cell-associated transmission of zoonotic gorilla SFV strains. We used flow-based cell cytometry and fluorescence microscopy to study envelope protein (Env) localization and the capacity of plasma antibodies to bind to infected cells. We visualized the cell-to-cell spread of SFV by real-time live imaging of a GFP-expressing prototype foamy virus (CI-PFV) strain. None of the samples neutralized cell-associated SFV infection, despite the inhibition of cell-free virus. We detected gorilla SFV Env in the perinuclear region, cytoplasmic vesicles and at the cell surface. We found that plasma antibodies bind to Env located at the surface of cells infected with primary gorilla SFV strains. Extracellular labeling of SFV proteins by human plasma samples showed patchy staining at the base of the cell and dense continuous staining at the cell apex, as well as staining in the intercellular connections that formed when previously connected cells separated from each other. In conclusion, SFV-specific antibodies from infected humans do not block cell-to-cell transmission, at least in vitro, despite their capacity to bind to the surface of infected cells. Trial registration: Clinical trial registration: www.clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03225794/. Author summary: Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. Simian foamy viruses (SFVs) can be transmitted to humans, in whom they establish persistent infection, as have the simian viruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus type 1 (HTLV-1). Such cross-species transmission of SFV is ongoing in many parts of the world where humans have contact with nonhuman primates. We previously showed high titers of neutralizing antibodies in the plasma of most SFV-infected individuals. These antiviral antibodies can inhibit cell-free virus entry. However, SFV efficiently spread from one cell to another. Here, we demonstrate that plasma antibodies do not block such cell-to-cell transmission, despite their capacity to bind to the surface of infected cells. In addition, we document for the first time the cell-to-cell spread of primary zoonotic gorilla SFV. [ABSTRACT FROM AUTHOR]

This review is an accompaniment to a Special Issue on "Retroviral RNA Processing". It discusses post-transcriptional regulation of retroviruses, ranging from the ancient foamy viruses to more modern viruses, such as HIV-1, HTLV-1, Rous sarcoma virus, murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus. This review is not comprehensive. However, it tries to address some of the major questions in the field with examples of how different retroviruses express their genes. It is amazing that a single primary RNA transcript can have so many possible fates: genomic RNA, unspliced mRNA, and up to 50 different alternatively spliced mRNAs. This review will discuss the sorting of RNAs for packaging or translation, RNA nuclear export mechanisms, splicing, translation, RNA modifications, and avoidance of nonsense-mediated RNA decay. [ABSTRACT FROM AUTHOR]

Varicella zoster virus (VZV) and simian varicella virus (SVV) cause varicella (chickenpox) in children and nonhuman primates, respectively. After resolution of acute disease, the viruses establish latent infection in neural ganglia, after which they may reactivate to cause a secondary disease, such as herpes zoster. SVV infection of nonhuman primates provides a model to investigate VZV pathogenesis and antiviral strategies. The VZV and SVV genomes are similar in size and structure and share 70–75% DNA homology. SVV and VZV DNAs are co-linear in gene arrangement with the exception of the left end of the viral genomes. Viral gene expression is regulated into immediate early, early, and late transcription during in vitro and in vivo infection. During viral latency, VZV and SVV gene expression is limited to transcription of a viral latency-associated transcript (VLT). VZV and SVV are closely related alphaherpesviruses that likely arose from an ancestral varicella virus that evolved through cospeciation into species-specific viruses. [ABSTRACT FROM AUTHOR]

Monkeypox is a rare zoonotic infection caused by monkey pox virus. It is an emerging disease which has become the most prevalent orthopoxvirus since the global eradication of smallpox in 1980. It is a mild illness which is mostly characterized by a prodromal of fever, malaise and progressive appearance of vesiculo-papular skin lesions. We report a case of a 30-year-old military personnel who was referred from 23 Brigade Medical Centre (BMC) to Federal Medical Centre (FMC) Yola on account of fever and progressive eruption of widespread skin rashes. Following isolation from suspicion of monkeypox, he was confirmed by PCR and managed symptomatically and fully recovered within two weeks of onset. His five close contacts did not develop any symptoms during the period of follow-up. This is the first confirmed case of monkeypox in the state. This case will trigger an awareness, amongst clinicians and surveillance officers in Adamawa State, of the existence of monkeypox and heighten the suspicion to promptly detect, isolate and treat more cases to halt transmission. [ABSTRACT FROM AUTHOR]

Background: Simian varicella virus (SVV) is a primate herpesvirus that causes a natural varicella‐like disease in Old World monkeys and may cause epizootics in facilities housing nonhuman primates. SVV infection of nonhuman primates is used as an experimental model to investigate varicella pathogenesis and to develop antiviral strategies. Methods: An indirect enzyme‐linked immunosorbent assay (ELISA) was developed to detect SVV antibodies in infected rhesus macaque monkeys. Results: An ELISA determined SVV antibody titers following experimental infection. SVV IgG was detected by day 14 post‐infection and remained elevated for at least 84 days. Conclusions: The SVV ELISA is a safe and rapid approach to confirm SVV seropositivity and to determine SVV antibody titers in naturally and experimentally SVV‐infected monkeys. In addition to being a useful diagnostic assay to rapidly confirm acute disease or past SVV infection, the SVV ELISA is a valuable epidemiological tool to determine the incidence of SVV in non‐human primate facilities. [ABSTRACT FROM AUTHOR]

Primary infection with varicella-zoster virus (VZV) causes varicella and the establishment of lifelong latency in sensory ganglion neurons. In one-third of infected individuals VZV reactivates from latency to cause herpes zoster, often complicated by difficult-to-treat chronic pain. Experimental infection of non-human primates with simian varicella virus (SVV) recapitulates most features of human VZV disease, thereby providing the opportunity to study the pathogenesis of varicella and herpes zoster in vivo. However, compared to VZV, the transcriptome and the full coding potential of SVV remains incompletely understood. Here, we performed direct long-read RNA sequencing to annotate the SVV transcriptome in lytically SVV-infected African green monkey (AGM) and rhesus macaque (RM) kidney epithelial cells. We refined structures of canonical SVV transcripts and uncovered numerous RNA isoforms, splicing events, fusion transcripts and non-coding RNAs, mostly unique to SVV. We verified the expression of canonical and newly identified SVV transcripts in vivo, using lung samples from acutely SVV-infected cynomolgus macaques. Expression of selected transcript isoforms, including those located in the unique left-end of the SVV genome, was confirmed by reverse transcription PCR. Finally, we performed detailed characterization of the SVV homologue of the VZV latency-associated transcript (VLT), located antisense to ORF61. Analogous to VZV VLT, SVV VLT is multiply spliced and numerous isoforms are generated using alternative transcription start sites and extensive splicing. Conversely, low level expression of a single spliced SVV VLT isoform defines in vivo latency. Notably, the genomic location of VLT core exons is highly conserved between SVV and VZV. This work thus highlights the complexity of lytic SVV gene expression and provides new insights into the molecular biology underlying lytic and latent SVV infection. The identification of the SVV VLT homolog further underlines the value of the SVV non-human primate model to develop new strategies for prevention of herpes zoster. Author summary: Varicella-zoster virus (VZV)–a ubiquitous human pathogen–infects most individuals during childhood, leading to chickenpox, after which the virus persists in the host for decades. Later in life, VZV reactivates to cause shingles, frequently associated with difficult-to-treat chronic pain. Our limited understanding of the viral life-cycle hampers the development of more effective treatment options. Simian varicella virus (SVV) is the non-human primate homologue of VZV and causes a natural disease in Old World monkeys with clinical, pathological, and immunological features resembling human VZV infection. However, it is unclear how similar both viruses are at the molecular level. Here, we have revisited the genome-wide transcriptional activity of SVV during lytic infection of kidney epithelial cells derived from two non-human primate species and validated expression of newly identified viral transcripts in lung tissue from SVV-infected animals. Together, this has led to the identification of numerous alternative RNA isoforms, mostly unique to SVV, and some of which may have functional implications for the virus. Notably, we defined the SVV latency-associated transcript, which is highly similar to its VZV counterpart. In conclusion, our study shows the value of understanding the molecular biology of a given animal model and identifies potentially conserved mechanism of latency. [ABSTRACT FROM AUTHOR]

The transition from an immature to a fully infectious mature retrovirus particle is associated with molecular switches that trigger dramatic conformational changes in the structure of the Gag proteins. A dominant maturation switch that stabilizes the immature capsid (CA) lattice is located downstream of the CA protein in many retroviral Gags. The HIV-1 Gag protein contains a stretch of 5 amino acid residues termed the "clasp motif," important for the organization of the hexameric subunits that provide stability to the overall immature HIV-1 shell. Sequence alignment of the CA C-terminal domains (CTDs) of HIV-1 and Mason-Pfizer monkey virus (MPMV) highlighted a spacer-like domain in M-PMV that may provide a comparable function. The importance of the sequences spanning the CA-nucleocapsid (NC) cleavage has been demonstrated by mutagenesis, but the specific requirements for the clasp motif in several steps of M-PMV particle assembly and maturation have not been determined in detail. In the present study, we report an examination of the role of the clasp motif in the M-PMV life cycle. We generated a series of M-PMV Gag mutants and assayed for assembly of the recombinant proteins in vitro and for the assembly, maturation, release, genomic RNA packaging, and infectivity of the mutant viruses in vivo. The mutants revealed major defects in virion assembly and release in HEK 293T and HeLa cells and even larger defects in infectivity. Our data identify the clasp motif as a fundamental contributor to CA-CTD interactions necessary for effi- cient retroviral infection. [ABSTRACT FROM AUTHOR]

The article focuses on eighteenth century's repeated attention to erotic, unsettling, and pronounced interspecies intimacies and fascination with a particular eye to the simian's erotic preponderance and its placement alongside the human. It mentions portrait induces a moment of mutual exchange and compatibility, which takes on erotic resonances given the monkey's physiology. It also mentions miniaturizes man, and becomes an index for Orientalism and an invocation of death.

One Shot for Lassa Virus: Up to 180 million people are at risk for infection with Lassa virus (LASV), and the endemic region for LASV is expanding. Thus, there is a critical need to develop a vaccine against LASV, preferably one that protects against multiple lineages of LASV, generates durable immune responses, and can be administered in a single dose. To that end, Mateo et al. investigated the ability of a recombinant measles virus vaccine expressing LASV proteins (MeV-NP) to protect nonhuman primates against multiple strains of LASV and to provide protection over a year after vaccination, showing that the vaccine was effective at both. MeV-NP, which is now in clinical trials, represents an advance in the field of LASV vaccine development. A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP). To evaluate vaccine efficacy against heterologous strains of Lassa virus, we challenged the monkeys a month later with heterologous strains from lineage II or lineage VII, finding that the vaccine was protective against these strains. A second cohort of monkeys was challenged 1 year later with the homologous Josiah strain, finding that a single dose of MeV-NP was sufficient to protect all vaccinated monkeys. These studies demonstrate that MeV-NP can generate both long-lasting immune responses and responses that are able to protect against diverse strains of Lassa virus. [ABSTRACT FROM AUTHOR]

Nonpathogenic retroviruses of the Spumaretrovirinae subfamily can persist long term in the cytoplasm of infected cells, completing their life cycle only after the nuclear membrane dissolves at the time of cell division. Since the targeting of slowly dividing cancer cells remains an unmet need in oncolytic virotherapy, we constructed a replication-competent foamy virus vector (oFV) from the genomes of two chimpanzee simian foamy viruses (PAN1 and PAN2) and inserted a green fluorescent protein (GFP) transgene in place of the bel-2 open reading frame. oFV-GFP infected and propagated with slow kinetics in multiple human tumor cell lines, inducing a syncytial cytopathic effect. Infection of growth-arrested MRC5 cells was not productive, but oFV genomes persisted in the cytoplasm, and the productive viral life cycle resumed when cell division was later restored. In vivo, the virus propagated extensively in intraperitoneal ovarian cancer xenografts, slowing tumor growth, significantly prolonging survival of the treated mice, and sustaining GFP transgene expression for at least 45 days. Our data indicate that oFV is a promising new replication-competent viral and gene delivery platform for efficient targeting of the most fundamental trait of cancer cells, their ability to sustain chronic proliferation. [ABSTRACT FROM AUTHOR]

The Democratic Republic of the Congo (DRC) has a history of nonhuman primate (NHP) consumption and exposure to simian retroviruses yet little is known about the extent of zoonotic simian retroviral infections in DRC. We examined the prevalence of human T-lymphotropic viruses (HTLV), a retrovirus group of simian origin, in a large population of persons with frequent NHP exposures and a history of simian foamy virus infection. We screened plasma from 3,051 persons living in rural villages in central DRC using HTLV EIA and western blot (WB). PCR amplification of HTLV tax and LTR sequences from buffy coat DNA was used to confirm infection and to measure proviral loads (pVLs). We used phylogenetic analyses of LTR sequences to infer evolutionary histories and potential transmission clusters. Questionnaire data was analyzed in conjunction with serological and molecular data. A relatively high proportion of the study population (5.4%, n = 165) were WB seropositive: 128 HTLV-1-like, 3 HTLV-2-like, and 34 HTLV-positive but untypeable profiles. 85 persons had HTLV indeterminate WB profiles. HTLV seroreactivity was higher in females, wives, heads of households, and increased with age. HTLV-1 LTR sequences from 109 persons clustered strongly with HTLV-1 and STLV-1 subtype B from humans and simians from DRC, with most sequences more closely related to STLV-1 from Allenopithecus nigroviridis (Allen's swamp monkey). While 18 potential transmission clusters were identified, most were in different households, villages, and health zones. Three HTLV-1-infected persons were co-infected with simian foamy virus. The mean and median percentage of HTLV-1 pVLs were 5.72% and 1.53%, respectively, but were not associated with age, NHP exposure, village, or gender. We document high HTLV prevalence in DRC likely originating from STLV-1. We demonstrate regional spread of HTLV-1 in DRC with pVLs reported to be associated with HTLV disease, supporting local and national public health measures to prevent spread and morbidity. Author summary: HTLV-1 is a human retrovirus of zoonotic simian origin that has spread globally causing inflammatory and carcinogenic disease. We previously showed that persons with high nonhuman primate (NHP) exposure in the Democratic Republic of the Congo (DRC) can be infected with another simian retrovirus, simian foamy virus (SFV), suggesting they are also at risk for infection with STLV-1. We conducted follow-up analysis of the same persons from rural villages of central DRC to determine exposure and transmission risks for STLV-1 and HTLV-1 infection. Most persons, especially women, reported high levels of NHP exposure. We identified possible introduction and spread of STLV-1 from a local monkey species across households, villages, and health zones in DRC. Most persons had HTLV-1 levels above those reported in previous studies for persons with disease. Our findings reveal that coordinated public health strategies are needed at both local and national levels to prevent further spread and morbidity of HTLV-1. [ABSTRACT FROM AUTHOR]

Archived jejunum tissue block specimens from control and simian immunodeficiency virus‐infected rhesus macaques are characterized using particle‐induced X‐ray emission (PIXE) in a MeV ion microprobe with 2 MeV protons. The results show considerable variance in the concentration of some elements (Ti, Mn, and Fe) between viremic and control tissue. Ti, Mn, and Fe are present at levels 50‐fold lower in samples from viremic versus control monkeys, a difference markedly higher than previously reported for infections. Pb and Ti are observed particularly in the crypts of both viremic and control jejunum samples. This is likely to be caused by ingestion of paint fragments picked from the cages used to house the animals. [ABSTRACT FROM AUTHOR]

Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus–infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection. [ABSTRACT FROM AUTHOR]

A distinguishing feature of the Mason-Pfizer monkey virus (MPMV) packaging signal RNA secondary structure is a single-stranded purine-rich sequence (ssPurines) in close vicinity to a palindromic stem loop (Pal SL) that functions as MPMV dimerization initiation site (DIS). However, unlike other retroviruses, MPMV contains a partially base-paired repeat sequence of ssPurines (bpPurines) in the adjacent region. Both purine-rich sequences have earlier been proposed to act as potentially redundant Gag binding sites to initiate the process of MPMV genomic RNA (gRNA) packaging. The objective of this study was to investigate the biological significance of ssPurines and bpPurines in MPMV gRNA packaging by systematic mutational and biochemical probing analyses. Deletion of either ssPurines or bpPurines individually had no significant effect on MPMV gRNA packaging, but it was severely compromised when both sequences were deleted simultaneously. Selective 2′ hydroxyl acylation analyzed by primer extension (SHAPE) analysis of the mutant RNAs revealed only mild effects on structure by deletion of either ssPurines or bpPurines, while the structure was dramatically affected by the two simultaneous deletions. This suggests that ssPurines and bpPurines play a redundant role in MPMV gRNA packaging, probably as Gag binding sites to facilitate gRNA capture and encapsidation. Interestingly, the deletion of bpPurines revealed an additional severe defect on RNA propagation that was independent of the presence or absence of ssPurines or the gRNA structure of the region. These findings further suggest that the bpPurines play an additional role in the early steps of MPMV replication cycle that is yet to be identified. [ABSTRACT FROM AUTHOR]