Transcriptional regulation of the HIV-1 inhibitory factor human mannose receptor 1 by the myeloid-specific transcription factor PU.1.

HIV-1 infection of human macrophages leads to the downmodulation of human mannose receptor 1 (hMRC1), a cell-surface glycoprotein that is involved in the host innate immune response. We previously reported that downmodulation of hMRC1 involves the transactivator of transcription (Tat)-dependent transcriptional silencing of the hMRC1 promoter. However, the inhibitory effect of Tat on hMRC1 transcription was indirect and involved inhibition of the transcriptional activator PU.

Human Mannose Receptor 1 Attenuates HIV-1 Infectivity in a Virus Isolate-Specific Manner.

Human mannose receptor 1 (hMRC1) is a transmembrane glycoprotein that belongs to the C-type lectin family and is expressed on the surface of most tissue macrophages. hMRC1 contributes to the binding and transmission of HIV-1 and is involved in the endocytic uptake of HIV-1 for subsequent antigen presentation. We previously reported that hMRC1 functions as an antiviral factor by inhibiting virus release through a BST-2-like mechanism.

HIV-1 Vpr Induces Degradation of Gelsolin, a Myeloid Cell-Specific Host Factor That Reduces Viral Infectivity by Inhibiting the Expression and Packaging of the HIV-1 Env Glycoprotein.

Gelsolin (GSN) is a structural actin-binding protein that is known to affect actin dynamics in the cell. Using mass spectrometry, we identified GSN as a novel Vpr-interacting protein. Endogenous GSN protein was expressed at detectable levels in monocyte-derived macrophages (MDM) and in THP-1 cells, but it was undetectable at the protein level in other cell lines tested.

4-phenylquinoline-8-amine induces HIV-1 reactivation and apoptosis in latently HIV-1 infected cells.

Combinational antiretroviral therapy (cART) dramatically suppresses the viral load to undetectable levels in human immunodeficiency virus (HIV)-infected patients. However, HIV-1 reservoirs in CD4+T cells and myeloid cells, which can evade cART and host antiviral immune systems, are still significant obstacles to HIV-1 eradication. The "Shock and Kill" approach using latently-reversing agents (LRAs) is therefore currently developing strategies for effective HIV-1 reactivation from latency and inducing cell death.

The Myeloid-Specific Transcription Factor PU.1 Upregulates Mannose Receptor Expression but Represses Basal Activity of the HIV-LTR Promoter.

Human mannose receptor 1 (MRC1) is a cell surface receptor expressed in macrophages and other myeloid cells that inhibits human immunodeficiency virus type 1 (HIV-1) particle release by tethering virions to producer cell membranes. HIV-1 counteracts MRC1 expression by inhibiting transcription. Here, we investigated the mechanism of MRC1 downregulation in HIV-1-infected macrophages.

Evaluation of the Geenius HIV 1/2 confirmatory assay for HIV-2 samples isolated in Japan.

Background: Although the number of HIV-2-infected individuals is quite low in Japan, at least three groups of HIV-2 (A, B and CRF01_AB) have been detected thus far. In particular, CRF01_AB HIV-2 cases have been found only in limited areas, Cote d'Ivoire and Japan. Here, we demonstrate that Geenius HIV 1/2 Confirmatory Assay (Geenius, Bio-Rad Laboratories) is able to detect HIV-2 samples, including groups A, B and CRF01_AB, isolated in Japan.

[Genomics and epidemiology of SARS-CoV-2 lineage].

Coronavirus disease 2019（COVID-19）is a newly emerging human infectious disease caused by severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）．It had been first identified in Wuhan at the end of 2019 and the spread of SARS-CoV-2 variants has become a crucial issue worldwide. WHO categorized SARS-CoV-2 variants as "Variants of Concern; VOCs" and "Variants of Interest; VOIs" based on transmissibility, disease severity or their susceptibility to vaccines. Especially, the spread of SARS-CoV-2 variant categorized in VOCs, such as B.

Inhibition of Vif-Mediated Degradation of APOBEC3G through Competitive Binding of Core-Binding Factor Beta.

Vif counteracts the host restriction factor APOBEC3G (A3G) and other APOBEC3s by preventing the incorporation of A3G into progeny virions. We previously identified Vif mutants with a dominant-negative (D/N) phenotype that interfered with the function of wild-type Vif, inhibited the degradation of A3G, and reduced the infectivity of viral particles by increased packaging of A3G. However, the mechanism of interference remained unclear, in particular since all D/N Vif mutants were unable to bind Cul5 and some mutants additionally failed to bind A3G, ruling out competitive binding to A3G or the E3 ubiquitin ligase complex as the sole mechanism.

Discovery of 4-oxoquinolines, a new chemical class of anti-HIV-1 compounds.

Antiretroviral therapy (ART) against HIV-1 infection offers the promise of controlling disease progression and prolonging the survival of HIV-1-infected patients. However, even the most potent ART regimens available today cannot cure HIV-1. Because patients will be exposed to ART for many years, physicians and researchers must anticipate the emergence of drug-resistant HIV-1, potential adverse effects of the current drugs, and need for future drug development.

Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages.

Apolipoprotein E (ApoE) belongs to a class of cellular proteins involved in lipid metabolism. ApoE is a polymorphic protein produced primarily in macrophages and astrocytes. Different isoforms of ApoE have been associated with susceptibility to various diseases including Alzheimer's and cardiovascular diseases.

Robust Enhancement of Lentivirus Production by Promoter Activation.

Lentiviral vectors are a valuable tool to deliver exogenous genes for stable expression in cells. While much progress has been made in processing lentiviral vector-containing culture medium, it remains to be explored how the production of lentiviral vector from producer cells can be increased. We initially found that co-expression of the SPRY domain-containing SOCS box protein 1 (SPSB1) promotes the production of human immunodeficiency virus type 1 (HIV-1) and lentiviral vector with increased expression of the Gag and envelope proteins and activation of the HIV-1 LTR and CMV promoter.

HIV-1 Vpr and p21 restrict LINE-1 mobility.

Long interspersed element-1 (LINE-1, L1) composes ∼17% of the human genome. However, genetic interactions between L1 and human immunodeficiency virus type 1 (HIV-1) remain poorly understood. In this study, we found that HIV-1 suppresses L1 retrotransposition.

Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages.

Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue macrophages, dendritic cells, and select lymphatic or liver endothelial cells. HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs) and is involved in the endocytic uptake of HIV-1 into these cells. Here, we identify hMRC1 as an antiviral factor that inhibits virus release through a bone marrow stromal antigen 2 (BST-2)-like mechanism.

Suppressor of cytokine signaling 1 counteracts rhesus macaque TRIM5α-induced inhibition of human immunodeficiency virus type-1 production.

Old world monkey TRIM5α is a host factor that restricts human immunodeficiency virus type-1 (HIV-1) infection. Previously, we reported that rhesus macaque TRIM5α (RhTRIM5α) restricts HIV-1 production by inducing degradation of precursor Gag. Since suppressor of cytokine signaling 1 (SOCS1) is known to enhance HIV-1 production by rescuing Gag from lysosomal degradation, we examined if SOCS1 is involved in RhTRIM5α-mediated late restriction.