Here we show that simian immunodeficiency virus (SIV) infection of rhesus macaques results in rapid upregulation of tetherin (BST-2 or CD317) on peripheral blood lymphocytes, including the CD4(+) CCR5(+) T cell targets of virus infection, with a peak of induction that coincides with peak alpha interferon (IFN-α) levels in plasma, and that tetherin remains above baseline levels throughout chronic infection. These observations are consistent with a role for tetherin in innate immunity to immunodeficiency virus infection.
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http://dx.doi.org/10.1128/JVI.01757-13 | DOI Listing |
PLoS Pathog
December 2024
University Hospital Erlangen, Institute of Clinical and Molecular Virology, Friedrich-Alexander Universität Erlangen-Nürnberg, Germany.
Broadly neutralizing antibodies (bnAbs) against HIV-1 have been shown to protect from systemic infection. When employing a novel challenge virus that uses HIV-1 Env for entry into target cells during the first replication cycle, but then switches to SIV Env usage, we demonstrated that bnAbs also prevented mucosal infection of the first cells. However, it remained unclear whether antibody Fc-effector functions contribute to this sterilizing immunity.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Center of Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, 119334 Russia.
The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.
View Article and Find Full Text PDFJ Virol
December 2024
Center of Infectious Diseases and Pathogen Biology, Institute of Virology and AIDS Research, Key Laboratory of Organ Regeneration and Transplantation of The Ministry of Education, The First Hospital of Jilin University, Changchun, China.
The Vpx protein encoded by HIV-2/simian immunodeficiency virus (SIV) can antagonize the restriction of the host intrinsic restriction factor, SAMHD1, in nondividing cells by promoting its polyubiquitination and subsequent degradation, thereby facilitating viral replication and immune evasion. However, the role of deubiquitinating enzymes (DUBs) in the dynamics of virus and host remains poorly understood. Here, we demonstrate that DUB USP37 significantly reverses the Vpx-mediated degradation of SAMHD1 in various HIV-2/SIV subtypes by interacting with SAMHD1 and removing its ubiquitin chains.
View Article and Find Full Text PDFJCI Insight
December 2024
Department of Pathology and.
African green monkeys (AGMs) are natural hosts of SIV whose infection does not progress to AIDS. Since early events of infection may be critical to pathogenesis in nonnatural hosts, we investigated early SIV infection in 29 adult male AGMs intrarectally inoculated with SIVsab92018 (SIVsab) and serially sacrificed throughout acute into early chronic infection to understand patterns of viral establishment, dissemination, and their effect on disease progression. Using this model, we showed that foci of virus replication could be detected at the site of inoculation and in the draining lymphatics as early as 1-3 days postinfection (dpi).
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates.
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