scholarly journals Inhibitory Effects of HIV-2 Vpx on Replication of HIV-1

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Mohamed Mahdi ◽  
Zsófia Szojka ◽  
János András Mótyán ◽  
József Tőzsér
Keyword(s):  
Cell Culture ◽  
Human Immunodeficiency Virus ◽  
Viral Protein ◽  
Dual Infection ◽  
Cellular Level ◽  
Potential Candidate ◽  
Accessory Gene ◽  
Immunodeficiency Virus ◽  
Protein X ◽  
Hiv 1

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) and HIV-2 share a striking genomic resemblance; however, variability in the genetic sequence accounts for the presence of unique accessory genes, such as the viral protein X (vpx) gene in HIV-2. Dual infection with both viruses has long been described in the literature, yet the molecular mechanism of how dually infected patients tend to do better than those who are monoinfected with HIV-1 has not yet been explored. We hypothesized that in addition to extracellular mechanisms, an HIV-2 accessory gene is the culprit, and interference at the viral accessory/regulatory protein level is perhaps responsible for the attenuated pathogenicity of HIV-1 observed in dually infected patients. Following simulation of dual infection in cell culture experiments, we found that pretransduction of cells with HIV-2 significantly protects against HIV-1 transduction. Importantly, we have found that this dampening of the infectivity of HIV-1 was a result of interviral interference carried out by viral protein X of HIV-2, resulting in a severe hindrance to the replication dynamics of HIV-1, influencing both its early and late phases of the viral life cycle. Our findings shed light on potential intracellular interactions between the two viruses and broaden our understanding of the observed clinical spectrum in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV-1.IMPORTANCEDual infection with human immunodeficiency virus types 1 and 2 is relatively common in areas of endemicity. For as-yet-unclarified reasons, patients who are dually infected were shown to have lower viral loads and generally a lower rate of progression to AIDS than those who are monoinfected. We aimed to explore dual infection in cell culture, to elucidate possible mechanisms by which HIV-2 may be able to exert such an effect. Our results indicate that on the cellular level, pretransduction of cells with HIV-2 significantly protects against HIV-1 transduction, which was found to be a result of interviral interference carried out by viral protein X of HIV-2. These findings broaden our knowledge of interviral interactions on the cellular level and may provide an explanation for the decreased pathogenicity of HIV-1 in dually infected patients, highlighting HIV-2 Vpx as a potential candidate worth exploring in the fight against HIV.

scholarly journals The Susceptibility of Primate Lentiviruses to Nucleosides and Vpx during Infection of Dendritic Cells Is Regulated by CA

2015 ◽  
Vol 89 (7) ◽  
pp. 4030-4034 ◽  
Author(s):  
Véronique Barateau ◽  
Xuan-Nhi Nguyen ◽  
Fanny Bourguillault ◽  
Grégory Berger ◽  
Stéphanie Cordeil ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Simian Immunodeficiency Virus ◽  
Viral Protein ◽  
Immunodeficiency Virus ◽  
Protein X ◽  
Primate Lentiviruses ◽  
Species Specific ◽  
Hiv 1

The block toward human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) can be relieved by Vpx (viral protein X), which degrades sterile alpha motif-hydroxylase domain 1 (SAMHD1) or by exogenously added deoxynucleosides (dNs), lending support to the hypothesis that SAMHD1 acts by limiting deoxynucleoside triphosphates (dNTPs). This notion has, however, been questioned. We show that while dNs and Vpx increase the infectivity of HIV-1, only the latter restores the infectivity of a simian immunodeficiency virus of macaques variant, SIVMACΔVpx virus. This distinct behavior seems to map to CA, suggesting that species-specific CA interactors modulate infection of DCs.

scholarly journals Antagonism to and Intracellular Sequestration of Human Tetherin by the Human Immunodeficiency Virus Type 2 Envelope Glycoprotein

2009 ◽  
Vol 83 (22) ◽  
pp. 11966-11978 ◽  
Author(s):  
Anna Le Tortorec ◽  
Stuart J. D. Neil
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Envelope Glycoprotein ◽  
Virus Assembly ◽  
Accessory Gene ◽  
Immunodeficiency Virus ◽  
T Cell Lines ◽  
Hiv 1 ◽  
Tetherin Antagonism

ABSTRACT Tetherin (CD317/BST-2), an interferon-induced membrane protein, restricts the release of nascent retroviral particles from infected cell surfaces. While human immunodeficiency virus type 1 (HIV-1) encodes the accessory gene vpu to overcome the action of tetherin, the lineage of primate lentiviruses that gave rise to HIV-2 does not. It has been previously reported that the HIV-2 envelope glycoprotein has a Vpu-like function in promoting virus release. Here we demonstrate that the HIV-2 Rod envelope glycoprotein (HIV-2 Rod Env) is a tetherin antagonist. Expression of HIV-2 Rod Env, but not that of HIV-1 or the closely related simian immunodeficiency virus (SIV) SIVmac1A11, counteracts tetherin-mediated restriction of Vpu-defective HIV-1 in a cell-type-specific manner. This correlates with the ability of the HIV-2 Rod Env to mediate cell surface downregulation of tetherin. Antagonism requires an endocytic motif conserved across HIV/SIV lineages in the gp41 cytoplasmic tail, but specificity for tetherin is governed by extracellular determinants in the mature Env protein. Coimmunoprecipitation studies suggest an interaction between HIV-2 Rod Env and tetherin, but unlike studies with Vpu, we found no evidence of tetherin degradation. In the presence of HIV-2 Rod Env, tetherin localization is restricted to the trans-Golgi network, suggesting Env-mediated effects on tetherin trafficking sequester it from virus assembly sites on the plasma membrane. Finally, we recapitulated these observations in HIV-2-infected CD4+ T-cell lines, demonstrating that tetherin antagonism and sequestration occur at physiological levels of Env expression during virus replication.

scholarly journals Novel Human Immunodeficiency Virus (HIV) Inhibitors That Have a Dual Mode of Anti-HIV Action

2003 ◽  
Vol 47 (10) ◽  
pp. 3109-3116 ◽  
Author(s):  
Miguel Stevens ◽  
Christophe Pannecouque ◽  
Erik De Clercq ◽  
Jan Balzarini
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protein Expression ◽  
Viral Protein ◽  
Green Fluorescence Protein Expression ◽  
Wide Range ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT We have found that novel pyridine oxide derivatives are inhibitors of a wide range of human immunodeficiency virus (HIV) type 1 (HIV-1) and HIV-2 strains in CEM cell cultures. Some of the compounds showed inhibitory activities against recombinant HIV-1 reverse transcriptase (RT), whereas others were totally inactive against this viral protein in vitro. Partial retention of anti-HIV-1 activity against virus strains that contain a variety of mutations characteristic of those for resistance to nonnucleoside RT inhibitors and a lack of inhibitory activity against recombinant HIV-2 RT suggested that these pyridine oxide derivatives possess a mode of antiviral action independent from HIV RT inhibition. Time-of-addition experiments revealed that these pyridine oxide derivatives interact at a postintegration step in the replication cycle of HIV. Furthermore, it was shown that these compounds are active not only in acutely HIV-1-infected cells but also in chronically HIV-infected cells. A dose-dependent inhibition of virus particle release and viral protein expression was observed upon exposure to the pyridine oxide derivatives. Finally, inhibition of HIV-1 long terminal repeat-mediated green fluorescence protein expression in quantitative transactivation bioassays indicated that the additional target of action of the pyridine oxide derivatives may be located at the level of HIV gene expression.

scholarly journals Production of Uninfectious Human Immunodeficiency Virus Type 1 Containing Viral Protein R Fused to a Single-Chain Antibody against Viral Integrase

1998 ◽  
Vol 72 (8) ◽  
pp. 6960-6964 ◽  
Author(s):  
Nobuo Okui ◽  
Noriko Kobayashi ◽  
Yoshihiro Kitamura
Keyword(s):  
Human Immunodeficiency Virus ◽  
Fusion Protein ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Protein ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A single-chain antibody (scAb) against human immunodeficiency virus type 1 (HIV-1) integrase was expressed as a fusion protein of scAb and HIV-1 viral protein R (Vpr), together with the HIV-1 genome, in human 293T cells. The expression did not affect virion production much but markedly reduced the infectivity of progeny virions. The fusion protein was found to be incorporated into the virions. The incorporation appears to account for the reduced infectivity.

scholarly journals Fruit-Specific Expression of the Human Immunodeficiency Virus Type 1 Tat Gene in Tomato Plants and Its Immunogenic Potential in Mice

2007 ◽  
Vol 14 (6) ◽  
pp. 685-692 ◽  
Author(s):  
Yuri Jorge Peña Ramírez ◽  
Ennio Tasciotti ◽  
Abel Gutierrez-Ortega ◽  
Alberto J. Donayre Torres ◽  
María Teresa Olivera Flores ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Tomato Fruit ◽  
Enzyme Linked Immunosorbent Assay ◽  
Potential Candidate ◽  
Tat Protein ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) Tat protein is considered a potential candidate vaccine antigen. In an effort to design a strategy for noninvasive vaccination against HIV-1, we developed transgenic tomatoes expressing the Tat protein. Two independent plants testing positive in transgene detection analysis were selected and grown to maturity. Monoclonal antibodies against Tat recognized a protein of the expected size. Interestingly, expression of Tat seemed to be toxic to the plant, as in all cases the fruit exhibited underdeveloped reproductive structures and no seeds. Nine groups of 10 pathogen-free BALB/c male mice were primed either orally, intraperitoneally, or intramuscularly with 10 mg of tomato fruit extract derived from transgenic or wild-type plants and with 10 μg of Tat86 recombinant protein. Mice were immunized at days 0, 14, and 28, and given boosters after 15 weeks; sera were drawn 7 days after each booster, and the antibody titer was determined by enzyme-linked immunosorbent assay. All three immunization approaches induced the development of a strong anti-Tat immunological response, which increased over time. Isotype subclass determination showed the presence of mucosal (immunoglobulin A) immunity soon after the beginning of the oral immunization protocol, and the data were confirmed by the presence of anti-Tat antibodies in fecal pellets and in vaginal washes. We also demonstrated that sera from immunized mice inhibited with high efficiency recombinant Tat-dependent transactivation of the HIV-1 long terminal repeat promoter. This neutralization activity might be relevant for the suppression of extracellular Tat activities, which play an important role in HIV disease development.

scholarly journals Viral protein X reduces the incorporation of mutagenic noncanonical rNTPs during lentivirus reverse transcription in macrophages

2019 ◽  
Vol 295 (2) ◽  
pp. 657-666
Author(s):  
Adrian Oo ◽  
Dong-Hyun Kim ◽  
Raymond F. Schinazi ◽  
Baek Kim
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Reverse Transcription ◽  
Viral Protein ◽  
Cell Types ◽  
Dntp Pool ◽  
Sam Domain ◽  
Primary Monocyte ◽  
Immunodeficiency Virus ◽  
Protein X ◽  
Hiv 1

Unlike activated CD4+ T cells, nondividing macrophages have an extremely small dNTP pool, which restricts HIV-1 reverse transcription. However, rNTPs are equally abundant in both of these cell types and reach much higher concentrations than dNTPs. The greater difference in concentration between dNTPs and rNTPs in macrophages results in frequent misincorporation of noncanonical rNTPs during HIV-1 reverse transcription. Here, we tested whether the highly abundant SAM domain– and HD domain–containing protein 1 (SAMHD1) deoxynucleoside triphosphorylase in macrophages is responsible for frequent rNTP incorporation during HIV-1 reverse transcription. We also assessed whether Vpx (viral protein X), an accessory protein of HIV-2 and some simian immunodeficiency virus strains that targets SAMHD1 for proteolytic degradation, can counteract the rNTP incorporation. Results from biochemical simulation of HIV-1 reverse transcriptase–mediated DNA synthesis confirmed that rNTP incorporation is reduced under Vpx-mediated dNTP elevation. Using HIV-1 vector, we further demonstrated that dNTP pool elevation by Vpx or deoxynucleosides in human primary monocyte-derived macrophages reduces noncanonical rNTP incorporation during HIV-1 reverse transcription, an outcome similarly observed with the infectious HIV-1 89.6 strain. Furthermore, the simian immunodeficiency virus mac239 strain, encoding Vpx, displayed a much lower level of rNTP incorporation than its ΔVpx mutant in macrophages. Finally, the amount of rNMPs incorporated in HIV-1 proviral DNAs remained unchanged for ∼2 weeks in macrophages. These findings suggest that noncanonical rNTP incorporation is regulated by SAMHD1 in macrophages, whereas rNMPs incorporated in HIV-1 proviral DNA remain unrepaired. This suggests a potential long-term DNA damage impact of SAMHD1-mediated rNTP incorporation in macrophages.

scholarly journals Nef-Mediated Resistance of Human Immunodeficiency Virus Type 1 to Antiviral Cytotoxic T Lymphocytes

2002 ◽  
Vol 76 (4) ◽  
pp. 1626-1631 ◽  
Author(s):  
Otto O. Yang ◽  
Phuong Thi Nguyen ◽  
Spyros A. Kalams ◽  
Tanya Dorfman ◽  
Heinrich G. Göttlinger ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cytotoxic T Lymphocytes ◽  
Complex Class ◽  
Accessory Gene ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Although Nef has been proposed to effect the escape of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTL) through downmodulation of major histocompatibility complex class I molecules, little direct data have been presented previously to support this hypothesis. By comparing nef-competent and nef-deleted HIV-1 strains in an in vitro coculture system, we demonstrate that the presence of this viral accessory gene leads to impairment of the ability of HIV-1-specific CTL clones to suppress viral replication. Furthermore, inhibition by genetically modified CTL that do not require major histocompatibility complex class I-presented antigen (expressing the CD4 T-cell receptor [TCR] ζ-chain hybrid receptor) is similar for both nef-competent and -deleted strains, indicating that Nef does not impair the effector functions of CTL but acts at the level of TCR triggering. In contrast, we note that another accessory gene, vpr, does not induce resistance of HIV-1 to suppression by CTL clones. We conclude that Nef (and not Vpr) contributes to functional HIV-1 immune evasion and that this effect is mediated by diminished antigen presentation to CTL.

scholarly journals Molecular Confirmation of Human Immunodeficiency Virus (HIV) Type 2 in HIV-Seropositive Subjects in South India

2000 ◽  
Vol 7 (6) ◽  
pp. 987-989 ◽  
Author(s):  
R. Kannangai ◽  
S. Ramalingam ◽  
K. J. Prakash ◽  
O. C. Abraham ◽  
R. George ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dual Infection ◽  
Test Results ◽  
Three Samples ◽  
Immunodeficiency Virus ◽  
Hiv Seropositive ◽  
Hiv 1 ◽  
Chiron Corporation

ABSTRACT Nested PCRs for human immunodeficiency virus type 1 (HIV-1) and HIV-2 were compared with immunoblot test results. Twelve of 13 immunoblot-positive HIV-2 samples were positive by PCR. There were five INNO-LIA (Innogenetics, Zwijnaarde, Belgium) and/or HIVBLOT 2.2 (Genelabs, Singapore) samples that tested positive for dual infection. HIV-1 PCR was positive in all samples, while HIV-2 PCR was positive in two and RIBA (Chiron Corporation, San Diego, Calif.) was positive for HIV-2 in three samples. Thus the prevalence of HIV-2 is accurately estimated by the use of immunoblotting, but that of HIV-1 and -2 dual infection may be overestimated.

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