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In vivo evolution of env in SHIV-AD8-infected rhesus macaques after AAV-vectored delivery of eCD4-Ig.
Mol Ther
December 2024
Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA. Electronic address:
eCD4-immunoglobulin (Ig) is an HIV entry inhibitor that mimics the engagement of both CD4 and CCR5 with the HIV envelope (Env) protein, a property that imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in SHIV-AD8-infected rhesus macaques (RMs) treated with adeno-associated virus vectors encoding eCD4-Ig.
View Article and Find Full Text PDFUtility of an Archival Dried Blood Spot (DBS) Collection from HIV-Infected Individuals with and without Cancer in a Resource-Limited Setting.
Int J Mol Sci
September 2024
Department of Medicine, University of California San Francisco, San Francisco, CA 94110, USA.
The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA.
View Article and Find Full Text PDFPhylogenetic evidence of extensive spatial mixing of diverse HIV-1 group M lineages within Cameroon but not between its neighbours.
Virus Evol
September 2024
Center of Research for Emerging and Re-Emerging Diseases (CREMER), Institute of Medical Research and Study of Medicinal Plants (IMPM), Yaoundé, PO Box. 906 Yaoundé, Cameroon.
From the perspective of developing relevant interventions for treating HIV and controlling its spread, it is particularly important to comprehensively understand the underlying diversity of the virus, especially in countries where the virus has been present and evolving since the cross-species transmission event that triggered the global pandemic. Here, we generate and phylogenetically analyse sequences derived from the (2010 bp; = 115), partial (345 bp; = 36), and (719 bp; = 321) genes of HIV-1 group M (HIV-1M) isolates sampled between 2000 and 2022 from two cosmopolitan cities and 40 remote villages of Cameroon. While 52.
View Article and Find Full Text PDFStructural and virologic mechanism of the emergence of resistance to M inhibitors in SARS-CoV-2.
Proc Natl Acad Sci U S A
September 2024
Department of Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan.
We generated SARS-CoV-2 variants resistant to three SARS-CoV-2 main protease (M) inhibitors (nirmatrelvir, TKB245, and 5h), by propagating the ancestral SARS-CoV-2 in VeroE6 cells with increasing concentrations of each inhibitor and examined their structural and virologic profiles. A predominant E166V-carrying variant (SARS-CoV-2), which emerged when passaged with nirmatrelvir and TKB245, proved to be resistant to the two inhibitors. A recombinant SARS-CoV-2 was resistant to nirmatrelvir and TKB245, but sensitive to 5h.
View Article and Find Full Text PDFEvolving molecular HIV clusters revealed genotype-specific dynamics in Guangzhou, China (2008-2020).
Int J Infect Dis
November 2024
School of Public Health and Management, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:
Objectives: This study investigated the genotype-specific dynamics of molecular HIV clusters (MHCs) in Guangzhou, China, aiming to enhance HIV control.
Methods: HIV pol sequences from people with HIV (PWH) in Guangzhou (2008-2020) were obtained for genotyping and molecular network creation. MHCs were identified and categorized into three types: emerging, growing, or stable.
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