Virus-host interactions play vital roles in viral replication and virus-induced pathogenesis. Viruses rely entirely upon host cells to reproduce progeny viruses; however, host factors positively or negatively regulate virus replication by interacting with viral proteins. The elucidation of virus-host protein interaction not only provides a better understanding of the molecular mechanisms by whi...

We constructed five chimeric clones between human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIVMAC) and four SIVMAC mutants by recombinant DNA techniques. Three chimeric clones and all mutants with an alteration in either the vif, vpx, vpr, or nef gene were infectious to human CD4-positive cell lines. The susceptibility of macaque monkey peripheral blood mononucle...

Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 d...

The deoxynucleoside triphosphohydrolase SAMHD1 restricts retroviral replication in myeloid cells. Human immunodeficiency virus type 2 (HIV-2) and a simian immunodeficiency virus from rhesus macaques (SIVmac) encode Vpx, a virion-packaged accessory protein that counteracts SAMHD1 by inducing its degradation. SAMHD1 is thought to work by depleting the pool of intracellular deoxynucleoside triphos...

The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutières syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SAMHD1 protein, the SAMHD1 gene was cloned, recombinant protein was produced, and the catalytic activ...

7 Department of Microbiology, Cancer Institute, Division of Infectious Disease, Department of 8 Medicine, and Department of Pathology, New York University School of Medicine, 9 522 First Ave, New York, NY 10016 10 11 12 13 Running title: HIV encoding Vpx 14 Abstract: 233 words 15 Text: 10,036 words 16 Corresponding author 17 Email: [email protected] 18 Phone 212-263-9197 19 Copyright...

The auxiliary/non-structural proteins of HIVcan be categorized into 2 groups, essential (Tat and Rev) and accessory (Vpr, Vpx, Vif, Vpu, and Nef). HIV replicates competently in vitro in T-cell lines without the need for accessory gene functions (Subbramanian and Cohen, 1994). However, in primary lymphocytes and macrophages, accessory gene products such as Vpr and Vpx contribute to the efficient...

We have established an assay for the function of preintegration complexes (PICs) of human immunodeficiency virus type 2 (HIV-2) to investigate the integration mechanism and to develop additional methods for screening candidate integration inhibitors. We partially purified HIV-2 PICs and found that they were competent to integrate viral cDNA into target DNA in vitro. Analysis of the structure of...

We have previously generated a macaque-tropic human immunodeficiency virus type 1 (HIV-1mt) clone designated MN4/LSDQgtu by genetic manipulation from a parental virus that replicates poorly in rhesus macaque cells. In rhesus cell line M1.3S and peripheral blood mononuclear cells (PBMCs), MN4/LSDQgtu grows comparably to a standard simian immunodeficiency virus clone derived from the rhesus macaq...

Analysis of rhesus macaques infected with a vpx deletion mutant virus of simian immunodeficiency virus mac239 (SIVΔvpx) demonstrates that Vpx is essential for efficient monocyte/macrophage infection in vivo but is not necessary for development of AIDS. To compare myeloid-lineage cell infection in monkeys infected with SIVΔvpx compared to SIVmac239, we analyzed lymphoid and gastrointestinal tiss...