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The global public health burden exerted by viruses partially stems from viruses’ ability to subdue host cells into creating an environment that promotes their multiplication (i.e., pro-viral). It has been discovered that viruses alter cell physiology by transferring viral material through extracellular vesicles (EVs), which serve as vehicles for intercellular communication. Here, we aim to provide a conceptual framework of all possible EV-virus associations and their resulting functions in infection output. First, we describe the different viral materials potentially associated with EVs by reporting that EVs can harbor entire virions, viral proteins and viral nucleic acids. We also delineate the different mechanisms underlying the internalization of these viral components into EVs. Second, we describe the potential fate of EV-associated viral material cargo by detailing how EV can circulate and target a naive cell once secreted. Finally, we itemize the different pro-viral strategies resulting from EV associations as the Trojan horse strategy, an alternative mode of viral transmission, an expansion of viral cellular tropism, a pre-emptive alteration of host cell physiology and an immunity decoy. With this conceptual overview, we aim to stimulate research on EV-virus interactions.

Among emerging zoonotic pathogens, mosquito-borne viruses (MBVs) circulate between vertebrate animals and mosquitoes and represent a serious threat to humans via spillover from enzootic cycles to the human community. Active surveillance of MBVs in their vectors is therefore essential to better understand and prevent spillover and emergence, especially at the human–animal interface. In this study, we assessed the presence of MBVs using molecular and phylogenetic methods in mosquitoes collected along an ecological gradient ranging from rural urbanized areas to highland forest areas in northern Thailand. We have detected the presence of insect specific flaviviruses in our samples, and the presence of the emerging zoonotic Tembusu virus (TMUV). Reported for the first time in 1955 in Malaysia, TMUV remained for a long time in the shadow of other flaviviruses such as dengue virus or the Japanese encephalitis virus. In this study, we identified two new TMUV strains belonging to cluster 3, which seems to be endemic in rural areas of Thailand and highlighted the genetic specificities of this Thai cluster. Our results show the active circulation of this emerging flavivirus in Thailand and the need for continuous investigation on this poorly known but threatening virus in Asia.

Background: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. Methods: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat–human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems. Results: Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively. Conclusions: The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.

Mayaro virus (MAYV) is an emergent alphavirus that causes MAYV fever. It is often associated with debilitating symptoms, particularly arthralgia and myalgia. MAYV infection is becoming a considerable health issue that, unfortunately, lacks a specific antiviral treatment. Favipiravir, a broad-spectrum antiviral drug, has recently been shown to exert anti-MAYV activity in vitro. In the present study, the potential of Favipiravir to inhibit MAYV replication in an in vivo model was evaluated. Immunocompetent mice were orally administrated 300 mg/kg/dose of Favipiravir at pre-, concurrent-, or post-MAYV infection. The results showed a significant reduction in infectious viral particles and viral RNA transcripts in the tissues and blood of the pre- and concurrently treated infected mice. A significant reduction in the presence of both viral RNA transcript and infectious viral particles in the tissue and blood of pre- and concurrently treated infected mice was observed. By contrast, Favipiravir treatment post-MAYV infection did not result in a reduction in viral replication. Interestingly, Favipiravir strongly decreased the blood levels of the liver disease markers aspartate- and alanine aminotransferase in the pre- and concurrently treated MAYV-infected mice. Taken together, these results suggest that Favipiravir is a potent antiviral drug when administered in a timely manner.

Aedes aegypti acts as a vector for several arboviral diseases that impose a major socio-economic burden. Moreover, the absence of a vaccine against these diseases and drug resistance in mosquitoes necessitates the development of new control strategies for vector-borne diseases. ABC transporters that play a vital role in immunity and other cellular processes in different organisms may act as non-canonical immune molecules against arboviruses, however, their role in mosquito immunity remains unexplored. This study comprehensively analyzed various genetic features of putative ABC transporters and classified them into A-H subfamilies based on their evolutionary relationships. Existing RNA-sequencing data analysis indicated higher expression of cytosolic ABC transporter genes (E & F Subfamily) throughout the mosquito development, while members of other subfamilies exhibited tissue and time-specific expression. Furthermore, comparative gene expression analysis from the microarray dataset of mosquito infected with dengue, yellow fever and West Nile viruses revealed 31 commonly expressed ABC transporters suggesting a potentially conserved transcriptomic signature of arboviral infection. Among these, only a few transporters of ABCA, ABCC and ABCF subfamily were upregulated, while most were downregulated. This indicates the possible involvement of ABC transporters in mosquito immunity.

Reported for the first time in 1955 in Malaysia, Tembusu virus (TMUV) remained, for a long time, in the shadow of flaviviruses with human health importance such as dengue virus or Japanese encephalitis virus. However, since 2010 and the first large epidemic in duck farms in China, the threat of its emergence on a large scale in Asia or even its spillover into the human population is becoming more and more significant. This review aims to report current knowledge on TMUV from viral particle organization to the development of specific vaccines and therapeutics, with a particular focus on host-virus interactions.

Chikungunya and Zika viruses, both transmitted by mosquito vectors, have globally re-emerged over for the last 60 years and resulted in crucial social and economic concerns. Presently, there is no specific antiviral agent or vaccine against these debilitating viruses. Understanding viral–host interactions is needed to develop targeted therapeutics. However, there is presently limited information in this area. In this review, we start with the updated virology and replication cycle of each virus. Transmission by similar mosquito vectors, frequent co-circulation, and occurrence of co-infection are summarized. Finally, the targeted host proteins/factors used by the viruses are discussed. There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses.

Mayaro virus (MAYV) and chikungunya virus (CHIKV) are known for their arthrotropism, but accumulating evidence shows that CHIKV infections are occasionally associated with serious neurological complications. However, little is known about the capacity of MAYV to invade the central nervous system (CNS). We show that human neural progenitors (hNPCs), pericytes and astrocytes are susceptible to MAYV infection, resulting in the production of infectious viral particles. In primary astrocytes, MAYV, and to a lesser extent CHIKV, elicited a strong antiviral response, as demonstrated by an increased expression of several interferon-stimulated genes, including ISG15, MX1 and OAS2. Infection with either virus led to an enhanced expression of inflammatory chemokines, such as CCL5, CXCL10 and CXCL11, whereas MAYV induced higher levels of IL-6, IL-12 and IL-15 in these cells. Moreover, MAYV was more susceptible than CHIKV to the antiviral effects of both type I and type II interferons. Taken together, this study shows that although MAYV and CHIKV are phylogenetically related, they induce different types of antiviral responses in astrocytes. This work is the first to evaluate the potential neurotropism of MAYV and shows that brain cells and particularly astrocytes and hNPCs are permissive to MAYV, which, consequently, could lead to MAYV-induced neuropathology.

Pediculus humanus capitis, the head louse, is an obligate blood-sucking ectoparasite that occurs in six divergent mitochondrial clades (A, D, B, F, C and E). Several studies reported the presence of different pathogenic agents in head lice specimens collected worldwide. These findings suggest that head louse could be a dangerous vector and a serious public health problem. Herein, we aimed to study the mitochondrial genetic diversity, the PHUM540560 gene polymorphisms profile of head lice collected in Guinea, as well as to screen for their associated pathogens. In 2018, a total of 155 head lice were collected from 49 individuals at the Medicals Centers of rural (Maférinyah village) and urban (Kindia city) areas, in Guinea. Specimens were subjected to a genetic analysis and pathogens screening using molecular tools. Results showed that all head lice belonged to eight haplotypes in the E haplogroup, with six newly identified for the first time. The study of the PHUM540560 gene polymorphisms of our clade E-head lice revealed that 82.5% exhibited the same polymorphism profile as the previously reported clade A-body lice. Screening for targeted pathogens revealed the presence of Acinetobacter spp., while sequencing highlighted the presence of several species, including Acinetobacter baumannii, Acinetobacter nosocomialis, Acinetobacter variabilis, Acinetobacter towneri and for the first time Acinetobacter haemolyticus. Our study is the first to report the existence of the Guinean haplogroup E, the PHUM540560 gene polymorphism profile as well as the presence of Acinetobacter species in head lice collected from Guinea.

Dynamics of dengue serotype 2 virus isolated from patients with different disease severity, namely flu-like classic dengue fever (DF) and dengue shock syndrome (DSS) were studied in its mosquito vector Aedes aegypti. We compared isolate infectivity and vector competence (VC) among thirty two A. aegypti-viral isolate pairs. Mosquito populations from high dengue incidence area exhibited overall greater VC than those from low dengue incidence area at 58.1% and 52.5%, respectively. On the other hand, the overall infection rates for the isolates ThNR2/772 (DF, 62.3%) and ThNR2/391 (DSS, 60.9%), were significantly higher than those for isolates ThNR2/406 (DF, 55.2%) and ThNR2/479 (DSS, 54.8%). These results suggest that the efficacy of dengue virus circulation was likely to vary according to the combination between the virus strains and origin of the mosquito strains, and this may have epidemiologic implications toward the incidence of flu-like classic dengue fever (DF) and dengue shock syndrome (DSS).

Mayaro virus (MAYV), isolated for the first time in Trinidad and Tobago, has captured the attention of public health authorities worldwide following recent outbreaks in the Americas. It has a propensity to be exported outside its original geographical range, because of the vast distribution of its vectors. Moreover, most of the world population is immunologically naïve with respect to infection with MAYV which makes this virus a true threat. The recent invasion of several countries by Aedesalbopictus underscores the risk of potential urban transmission of MAYV in both tropical and temperate regions. In humans, the clinical manifestations of MAYV disease range from mild fever, rash, and joint pain to arthralgia. In the absence of a licensed vaccine and clinically proven therapeutics against Mayaro fever, prevention focuses mainly on household mosquito control. However, as demonstrated for other arboviruses, mosquito control is rather inefficient for outbreak management and alternative approaches to contain the spread of MAYV are therefore necessary. Despite its strong epidemic potential, little is currently known about MAYV. This review addresses various aspects of MAYV, including its epidemiology, vector biology, mode of transmission, and clinical complications, as well as the latest developments in MAYV diagnosis.

While the Zika virus (ZIKV) 2014–2017 pandemic has subsided, there remains active transmission. Apart from horizontal transmission to humans, the main vector Aedes aegypti can transmit the virus vertically from mother to offspring. Large variation in vertical transmission (VT) efficiency between studies indicates the influence of parameters, which remain to be characterized. To determine the roles of extrinsic incubation time and gonotrophic cycle, we deployed an experimental design that quantifies ZIKV in individual progeny and larvae. We observed an early infection of ovaries that exponentially progressed. We quantified VT rate, filial infection rate, and viral load per infected larvae at 10 days post oral infection (d.p.i.) on the second gonotrophic cycle and at 17 d.p.i. on the second and third gonotrophic cycle. As compared to previous reports that studied pooled samples, we detected a relatively high VT efficiency from 1.79% at 10 d.p.i. and second gonotrophic cycle to 66% at 17 d.p.i. and second gonotrophic cycle. At 17 d.p.i., viral load largely varied and averaged around 800 genomic RNA (gRNA) copies. Longer incubation time and fewer gonotrophic cycles promoted VT. These results shed light on the mechanism of VT, how environmental conditions favor VT, and whether VT can maintain ZIKV circulation.

Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipid recognition protein (ML26A) transcripts, as compared to Ae. albopictus. Increased expression levels of thio-ester-containing protein 22 (TEP22) and Niemann−Pick type C1 (NPC1) gene transcripts were observed in infected Ae. albopictus, but not Ae. aegypti. The differences in these gene expression levels during MAYV infection could explain the variation in susceptibility observed in both mosquito species.

Mayaro virus (MAYV) is an emerging arthritogenic alphavirus belonging to the Togaviridae family. Infection leads to a dengue-like illness accompanied by severe polyarthralgia. However, the molecular and cellular mechanisms of arthritis as a result of MAYV infection remain poorly understood. In the present study, we assess the susceptibility of human chondrocytes (HC), fibroblast-like synoviocytes and osteoblasts that are the major cell types involved in osteoarthritis, to infection with MAYV. We show that these cells are highly permissive to MAYV infection and that viral RNA copy number and viral titers increase over time in infected cells. Knowing that HC are the primary cells in articular cartilage and are essential for maintaining the cartilaginous matrix, gene expression studies were conducted in MAYV-infected primary HC using polymerase chain reaction (PCR) arrays. The infection of the latter cells resulted in an induction in the expression of several matrix metalloproteinases (MMP) including MMP1, MMP7, MMP8, MMP10, MMP13, MMP14 and MMP15 which could be involved in the destruction of articular cartilage. Infected HC were also found to express significantly increased levels of various IFN-stimulated genes and arthritogenic mediators such as TNF-α and IL-6. In conclusion, MAYV-infected primary HC overexpress arthritis-related genes, which may contribute to joint degradation and pathogenesis.