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Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma‐associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV‐1 TAT protein can be essential in developing AIDS‐associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV‐specific TAT profile among PLHIV who developed KS. [ABSTRACT FROM AUTHOR]

Pulchellin is a plant biotoxin categorized as a type 2 ribosome-inactivating protein (RIPs) which potentially kills cells at very low concentrations. Biotoxins serve as targeting immunotoxins (IT), consisting of antibodies conjugated to toxins. ITs have two independent protein components, a human antibody and a toxin with a bacterial or plant source; therefore, they pose unique setbacks in immunogenicity. To overcome this issue, the engineering of epitopes is one of the beneficial methods to elicit an immunological response. Here, we predicted the tertiary structure of the pulchellin A-chain (PAC) using five common powerful servers and adopted the best model after refining. Then, predicted structure using four distinct computational approaches identified conformational B-cell epitopes. This approach identified some amino acids as a potential for lowering immunogenicity by point mutation. All mutations were then applied to generate a model of pulchellin containing all mutations (so-called PAM). Mutants' immunogenicity was assessed and compared to the wild type as well as other mutant characteristics, including stability and compactness, were computationally examined in addition to immunogenicity. The findings revealed a reduction in immunogenicity in all mutants and significantly in N146V and R149A. Furthermore, all mutants demonstrated remarkable stability and validity in Molecular Dynamic (MD) simulations. During docking and simulations, the most homologous toxin to pulchellin, Abrin-A was applied as a control. In addition, the toxin candidate containing all mutations (PAM) disclosed a high level of stability, making it a potential model for experimental deployment. In conclusion, by eliminating B-cell epitopes, our computational approach provides a potential less immunogenic IT based on PAC. [ABSTRACT FROM AUTHOR]

Entry of human immunodeficiency type 1 virus (HIV-1) into target cells requires both CD4and one of the chemokine receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 and CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. A 32-nucleotide deletion (delta32) within the beta-chemokine receptor 5 gene (CCR5) has been described in subjects who remain uninfected despite extensive exposition to HIV-1. The heterozygous genotype delays disease progression. This allele is common among Caucasians, but has not been found in people of African or Asian ancestry. A more common transition involving a valine to isoleucine switch in transmembrane domain I of CCR2B (64I), with unknown functional consequences, was found to delay disease progression but not to reduce infection risk. As the Brazilian population consists of a mixture of several ethnic groups, we decided to examine the genotype frequency of these polymorphisms in this country. There were 11.5% CCR5 heterozygotes among the HIV-1 infected population and 12.5% among uninfected individuals, similar to data from North America and Western Europe. The prevalence of CCR2-64I homozygotes and heterozygotes was 0.06 and 15.2%, respectively, also similar to what is known for North America and Western Europe.

Melanoma is an aggressive skin cancer that affects approximately 140,000 people worldwide each year, with a high fatality rate. Available treatment modalities show limited efficacy in more severe cases. Hence, the search for new treatment modalities, including immunotherapies, for curing, mitigating, and/or preventing cancer is important and urgently needed. Carbon nanoparticles associated with some plant materials, such as Aloe vera, have shown appealing antineoplastic activity, derived mainly from the compounds aloin, aloe-emodin, barbaloin acemannan, and octapeptide, thus representing new possibilities as antitumor agents. This systematic review aims to arouse interest and present the possibilities of using Aloe vera combined with carbon-based nanomaterials as an antineoplastic agent in the treatment and prevention of melanoma. Limitations and advances in melanoma treatment using functionalized carbon nanomaterials are discussed here. Moreover, this review provides the basis for further studies designed to fully explore the potential of carbon nanomaterials associated with Aloe vera in the treatment of various cancers, with a focus on melanoma. [ABSTRACT FROM AUTHOR]

Circular single stranded DNA viruses (CRESS DNA) encoding a homologous replication-associated protein (REP) have been identified in most of eukaryotic groups. It is not clear yet the role in human diseases or details of the life cycle of these viruses. Recently, much interest has been raised in the evolutionary history of CRESS DNA owing to the increasing number of new sequences obtained by Next-Generation Sequencing (NGS) in distinct host species. In this study we describe two full-length CRESS DNA genomes obtained of two newly diagnosed HIV patients from São Paulo State, Brazil. The initial BLASTx search indicated that both sequences (named SP-FFB/2020 and SP-MJMS/2020) are highly similar (98%) to a previous CRESS DNA sequence detected in human fecal sample from Peru in 2016 and designated as pecovirus (Peruvian stool-associated circo-like virus). This study reported for the first time the Human feces pecovirus in the feces of two newly diagnosed HIV patients in Brazil. Our comparative analysis showed that although pecoviruses in South America share an identical genome structure they diverge and form distinct clades. Thus, we suggest the circulation of different species of pecoviruses in Latin America. Nevertheless, further studies must be done to examine the pathogenicity of this virus. [ABSTRACT FROM AUTHOR]

This study characterized HIV-1 among antiretroviral-naive populations presenting recent infection (RI) or long-standing infection (LSI). Sera collected from January 1999 to December 2001 at an anonymous HIV testing site in Santos, Brazil, were submitted to serologic testing algorithm for recent HIV seroconversion (STARHS). The STARHS methodology uses a combination of a sensitive and a less sensitive version of an anti-HIV enzyme immunoassay (EIA), and specimens found to be positive on the sensitive EIA and negative on the less sensitive EIA are considered to represent RI. HIV-1 V3 and pol regions of those with RI and LSI were compared. Antiretroviral resistance was defined solely by genotypic analysis. Ninety samples were evaluated representing those taken from an original cohort of 345 individuals, for whom adequate samples were available. Of 90 HIV-positive individuals, 25 presented RI. Cumulatively, 36.8% of those with RI and 25% of those with LSI presented resistance to at least one antiretroviral class. In the pol and V3 regions, 47% and 53% of those with RI presented clade B viruses and B/F recombinant viruses, respectively, whereas 56.2% , 41.7%, and 2.1% of those with LSI harbored clades B, B/F, and clade C viruses, respectively. Primary resistance and the prevalence of B/F recombinants was high in this population. Monitoring HIV-1 genetic diversity is important for developing vaccines and treatment strategies.

Viral suppression after antiretroviral therapy is monitored by determining plasma HIV-1 through viral load assays. However, such assays only provide HIV-1 replication rates at the moment samples are drawn and do not reflect any trend in viremia fluctuation preceding sample collection. The objective of this study was to correlate the optical density (OD) of the less sensitive HIV-1 enzyme immunoassay (EIA), used in the serologic testing algorithm for recent HIV seroconversion, with viral loads in a group of HIV-infected patients on antiretroviral therapy. We studied samples from 20 previously antiretroviral-naive subjects treated with the zidovudine-lamivudine combination plus indinavir for a 20-week period. Viral loads were assessed using the less sensitive HIV-1 EIA at baseline and at 4-week intervals. There was a strong correlation between lower OD and viral load after introduction of antiretroviral drugs (p < 0.01). The ODs tended to decrease in parallel with drops in viral loads and remain steady when viral loads did not change significantly. These results suggest that the less sensitive HIV-1 EIA may be used as a complementary method for monitoring the efficacy of antiretroviral therapy, with special appeal in resource-poor areas where health professionals have limited laboratory expertise.

We describe drug-resistance mutation dynamics of the gag gene among individuals under antiretroviral virologic failure who underwent analytical treatment interruption (ATI). These mutations occur in and around the cleavage sites that form the particles that become the mature HIV-1 virus. The study involved a 12-week interruption in antiretroviral therapy (ART) and sequencing of the gag gene in 38 individuals experiencing virologic failure and harboring triple-class resistant HIV strains. Regions of the gag gene surrounding the NC-p2 and p1-p6 cleavage sites were sequenced at baseline before ATI and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Fourteen of the sixteen patients sequenced presented at least one mutation in the gag gene at baseline, with an average of 4.93 mutations per patient. All the mutations had reverted to the wild type by the end of the study. Mutations in the gag gene complement mutations in the pol gene to restore HIV fitness. Those mutations around cleavage sites and within substrates contribute to protease inhibitor resistance and difficulty in re-establishing effective virologic suppression. ART interruption in the presence of antiretroviral resistant HIV strains was used here as a practical measure for more adapted HIV profiles in the absence of ART selective pressure. [ABSTRACT FROM AUTHOR]

Research has been conducted on HIV-1 incidence and genetic subtype prevalence among cocaine users in Brazil. Results demonstrate that there is no association between specific route of drug administration and HIV-1 subtype and that there is evidence of recent HIV-1 transmission among non injecting cocaine users.

Different light-based strategies have been investigated to inactivate viruses. Herein, we developed an HIV-based pseudotyped model of SARS-CoV-2 (SC2) to study the mechanisms of virus inactivation by using two different strategies; photoinactivation (PI) by UV-C light and photodynamic inactivation (PDI) by Photodithazine photosensitizer (PDZ). We used two pseudoviral particles harboring the Luciferase-IRES-ZsGreen reporter gene with either a SC2 spike on the membrane or without a spike as a naked control pseudovirus. The mechanism of viral inactivation by UV-C and PDZ-based PDI were studied via biochemical characterizations and quantitative PCR on four levels; free-cell viral damage; viral cell entry; DNA integration; and expression of reporter genes. Both UV-C and PDZ treatments could destroy single stranded RNA (ssRNA) and the spike protein of the virus, with different ratios. However, the virus was still capable of binding and entering into the HEK 293T cells expressing angiotensin-converting enzyme 2 (ACE-2). A dose-dependent manner of UV-C irradiation mostly damages the ssRNA, while PDZ-based PDI mostly destroys the spike and viral membrane in concentration and dose-dependent manners. We observed that the cells infected by the virus and treated with either UV-C or PDZ-based PDI could not express the luciferase reporter gene, signifying the viral inactivation, despite the presence of RNA and DNA intact genes. [ABSTRACT FROM AUTHOR]

This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management. [ABSTRACT FROM AUTHOR]