Primary Human Immunodeficiency Virus Type 2 (HIV-2) Isolates, Like HIV-1 Isolates, Frequently Use CCR5 but Show Promiscuity in Coreceptor Usage

Mörner, Andreas; Björndal, Åsa; Albert, Jan; KewalRamani, Vineet N.; Littman, Dan R.; Inoue, Rie; Thorstensson, Rigmor; Fenyõ, Éva Mária; Björling, Ewa

doi:10.1128/jvi.73.3.2343-2349.1999

Cited by 295 publications

(94 citation statements)

References 47 publications

(69 reference statements)

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“…The following reagents were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: (GHOST (3) R3/X4/R5; Cat. 3943) from Dr. Vineet N. KewalRamani and Dr. Dan R. Littman [80].…”

Section: Cells and Cell Linesmentioning

confidence: 99%

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Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export

et al. 2014

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BackgroundType I interferon (IFN) inhibits virus replication by activating multiple antiviral mechanisms and pathways. It has long been recognized that type I IFNs can potently block HIV-1 replication in vitro; as such, HIV-1 has been used as a system to identify and characterize IFN-induced antiviral proteins responsible for this block. IFN-induced HERC5 contains an amino-terminal Regulator of Chromosome Condensation 1 (RCC1)-like domain and a carboxyl-terminal Homologous to the E6-AP Carboxyl Terminus (HECT) domain. HERC5 is the main cellular E3 ligase that conjugates the IFN-induced protein ISG15 to proteins. This E3 ligase activity was previously shown to inhibit the replication of evolutionarily diverse viruses, including HIV-1. The contribution of the RCC1-like domain to the antiviral activity of HERC5 was previously unknown.ResultsIn this study, we showed that HERC5 inhibits HIV-1 particle production by a second distinct mechanism that targets the nuclear export of Rev/RRE-dependent RNA. Unexpectedly, the E3 ligase activity of HERC5 was not required for this inhibition. Instead, this activity required the amino-terminal RCC1-like domain of HERC5. Inhibition correlated with a reduction in intracellular RanGTP protein levels and/or the ability of RanGTP to interact with RanBP1. Inhibition also correlated with altered subcellular localization of HIV-1 Rev. In addition, we demonstrated that positive evolutionary selection is operating on HERC5. We identified a region in the RCC1-like domain that exhibits an exceptionally high probability of having evolved under positive selection and showed that this region is required for HERC5-mediated inhibition of nuclear export.ConclusionsWe have identified a second distinct mechanism by which HERC5 inhibits HIV-1 replication and demonstrate that HERC5 is evolving under strong positive selection. Together, our findings contribute to a growing body of evidence suggesting that HERC5 is a novel host restriction factor.

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Section: Cells and Cell Linesmentioning

confidence: 99%

“…Alternatively, the clarified supernatants were used to infect GHOST(3(3)R3/X4/R5 indicator cells. Quantification of infectious virus release using GHOST(3)R3/X4/R5 indicator cells has been described previously [80].…”

Section: Quantification Of Infectious Virusmentioning

confidence: 99%

Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export

et al. 2014

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“…Stable clones were selected in DMEM medium containing 5 mM L-histidinol (Sigma-Aldrich., St. Louis, MO) and cloned by limiting dilution assay. GHOST cell medium was supplemented with 0.2 mg/ml G418, 0.1 mg/ml hygromycin B and 1 mg/ml puromycin (Sigma) as previously described [76].…”

Section: Cell Culturementioning

confidence: 99%

Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag

et al. 2010

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BackgroundThe Pr55gag (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown. Upon activation, CD4+ T cells, the primary target of HIV infection, express the class II transcriptional activator (CIITA) and therefore the MHC class II isotype, HLA-DR. Similar to Gag, HLA-DR localizes to the PM and at the membranes of endosomes and specialized vesicular MHC class II compartments (MIICs). In HIV producer cells, transient HLA-DR expression induces intracellular Gag accumulation and impairs virus release.Methodology/Principal FindingsHere we demonstrate that both stable and transient expression of CIITA in HIV producer cells does not induce HLA-DR-associated intracellular retention of Gag, but does increase the infectivity of virions. However, neither of these phenomena is due to recapitulation of the class II antigen presentation pathway or CIITA-mediated transcriptional activation of virus genes. Interestingly, we demonstrate that CIITA, apart from its transcriptional effects, acts cytoplasmically to enhance Pr160gag-pol (Gag-Pol) levels and thereby the viral protease and Gag processing, accounting for the increased infectivity of virions from CIITA-expressing cells.Conclusions/SignificanceThis study demonstrates that CIITA enhances HIV Gag processing, and provides the first evidence of a novel, post-transcriptional, cytoplasmic function for a well-known transactivator.

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“…African green monkey kidney cells (COS-1) were obtained from the American Type Culture Collection. The HOS-CD4/LTR-hGFP (GHOST) cell line, which expresses green fluorescent protein (GFP) under the control of the HIV type 2 (HIV-2) long terminal repeat (LTR), was obtained though the AIDS Reference and Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, and was originally contributed by Vineet N. KewalRamani and Dan R. Littman (7,44). Cells were maintained in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum (Sigma), 10 U of penicillin G sodium/ml, and 10 g of streptomycin sulfate/ml (Pen-Strep; GibcoBRL).…”

Section: Cell and Transfectionsmentioning

confidence: 99%

Activity of the Mason-Pfizer Monkey Virus Fusion Protein Is Modulated by Single Amino Acids in the Cytoplasmic Tail

Cao

Micoli

Hunter

2005

J Virol

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Mason-Pfizer monkey virus (M-PMV) encodes a transmembrane glycoprotein with a 38-amino-acid-long cytoplasmic tail. After the release of the immature virus, a viral protease-mediated cleavage of the cytoplasmic tail (CT) results in the loss of 17 amino acids from the carboxy terminus and renders the envelope protein fusion competent. To investigate the role of individual amino acid residues in the CT in fusion, a series of mutations was introduced, and the effects of these mutations on glycoprotein biosynthesis and fusion were examined. Most of the alanine-scanning mutations in the CT had little effect on fusion activity. However, four amino acid substitutions (threonine 4, lysine 7, glutamine 9, and isoleucine 10) resulted in substantially increased fusogenicity, while six (leucine 2, phenylalanine 5, isoleucine 13, lysine 16, proline 17, and glycine 31) resulted in much-reduced fusion. Interestingly, the bulk of these mutations are located upstream of the CT cleavage site in a region that has the potential to form a coiled-coil in the Env trimer. Substitutions at glutamine 9 and isoleucine 10 with alanine had the most dramatic positive effect and resulted in the formation of large syncytia. Taken together, these data demonstrate that individual residues within the cytoplasmic domain of M-PMV Env can modulate, in both a positive and negative manner, biological functions that are associated with the extracellular domains of the glycoprotein complex.The glycoprotein complex of retroviruses consists of two polypeptides: the external, highly glycosylated, hydrophilic, surface (SU) glycoprotein and the transmembrane or TM glycoprotein. The glycoproteins are initially translated as a polyprotein precursor from a spliced envelope (env) gene-specific mRNA. The polyprotein precursor Env is proteolytically cleaved during its transport through the Golgi complex to the plasma membrane of the cell (19,28,30,58,75). While Env proteins are not required for the formation of virus particles, they play an important role in the virus replication cycle. The SU glycoprotein is responsible for receptor binding for the virus, whereas the TM glycoprotein is responsible for anchoring the SU protein at the surface of the infected cell or the virus membrane (30,41,48,61). The TM glycoprotein also mediates virus-cell membrane fusion during virus entry as well as cell-cell fusion via a fusion peptide and heptad repeat motifs that are located in the extracellular domain (15,64,72). The two heptad repeat regions located in the TM proteins of viruses such as paramyxovirus (6,9,33,53), influenza virus (73), coronavirus (13, 39), and retroviruses (23, 24) have been shown to play an essential role in viral fusion and infectivity (10,15,25,59,64,70).The glycoproteins of different retroviruses have structural similarity while their sizes and amino acid compositions differ. The amino terminus of the Env precursors contains the signal peptide, a short stretch of hydrophobic amino acids that directs the entry of the newly synthesized env gene protein ...

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Primary Human Immunodeficiency Virus Type 2 (HIV-2) Isolates, Like HIV-1 Isolates, Frequently Use CCR5 but Show Promiscuity in Coreceptor Usage

Cited by 295 publications

References 47 publications

Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export

Interferon-induced HERC5 is evolving under positive selection and inhibits HIV-1 particle production by a novel mechanism targeting Rev/RRE-dependent RNA nuclear export

Class II Transactivator (CIITA) Enhances Cytoplasmic Processing of HIV-1 Pr55Gag

Activity of the Mason-Pfizer Monkey Virus Fusion Protein Is Modulated by Single Amino Acids in the Cytoplasmic Tail

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