Search

Introduction: Human pegivirus-1 (HPgV-1) influences the pathogenesis and outcome of viral infections. We investigated the prevalence and impact of HPgV-1 due to the paucity of studies on Indian people living with HIV (PLHIV). Methodology: Samples were collected from 347 treatment-naïve PLHIV; and 100 blood donors negative for HIV, HBV, and HCV. CD4+ T- cell and HIV-1 viral load were measured using flow-cytometry and quantitative polymerase chain reaction (qPCR), respectively. HPgV-1 was quantified and genotyped by qPCR and Sanger sequencing, respectively. Results: HPgV-1 viremia in PLHIV and controls was 11% (38/347) and 1% (1/100), respectively. We found HPgV-1 genotype-2a in PLHIV and genotype-2b in controls. Male preponderance was seen in HIV-1 mono-infection and co-infection groups (166 vs. 143 and 33 vs. 5; p < 0.0001). The peak prevalence of HPgV-1 was at 31--50 years (p = 0.02). CD4+ T-cell count (245.5 vs. 240; p = 0.59) and HIV-1 log viral load (4.7 vs. 4.9; p = 0.50) were not significantly different between the HIV-1 mono-infected and coinfected individuals. However, a direct correlation existed between HpgV-1 viral load and CD4+ T-cell count (r = 0.27, p = 0.05) and an inverse correlation with HIV-1 viral load (r = -0.21, p = 0.10). Conclusions: This is the first study in India to estimate the HPgV-1 prevalence in PLHIV with the predominance of genotype-2a. HPgV-1 viremia had a moderate impact on CD4+ T-cells and HIV-1 viral load, which requires a longitudinal study to identify the beneficial influence on HIV-1 disease progression and outcome. [ABSTRACT FROM AUTHOR]

Background: Monkeypox (Mpox) is an important human pathogen without etiological treatment. A viral-host interactome study may advance our understanding of molecular pathogenesis and lead to the discovery of suitable therapeutic targets., Methods: GEO Expression datasets characterizing mRNA profile changes in different host responses to poxviruses were analyzed for shared pathway identification, and then, the Protein-protein interaction (PPI) maps were built. The viral gene expression datasets of Monkeypox virus (MPXV) and Vaccinia virus (VACV) were used to identify the significant viral genes and further investigated for their binding to the library of targeting molecules., Results: Infection with MPXV interferes with various cellular pathways, including interleukin and MAPK signaling. While most host differentially expressed genes (DEGs) are predominantly downregulated upon infection, marked enrichments in histone modifiers and immune-related genes were observed. PPI analysis revealed a set of novel virus-specific protein interactions for the genes in the above functional clusters. The viral DEGs exhibited variable expression patterns in three studied cell types: primary human monocytes, primary human fibroblast, and HeLa, resulting in 118 commonly deregulated proteins. Poxvirus proteins C6R derived protein K7 and K7R of MPXV and VACV were prioritized as targets for potential therapeutic interventions based on their histone-regulating and immunosuppressive properties. In the computational docking and Molecular Dynamics (MD) experiments, these proteins were shown to bind the candidate small molecule S3I-201, which was further prioritized for lead development., Results: MPXV circumvents cellular antiviral defenses by engaging histone modification and immune evasion strategies. C6R-derived protein K7 binding candidate molecule S3I-201 is a priority promising candidate for treating Mpox., (© 2024. The Author(s).)