scholarly journals Characterization of a Novel vpu-Harboring Simian Immunodeficiency Virus from a Dent's Mona Monkey (Cercopithecus mona denti)

2005 ◽  
Vol 79 (13) ◽  
pp. 8560-8571 ◽  
Author(s):  
Marie-Christine Dazza ◽  
Michel Ekwalanga ◽  
Monique Nende ◽  
Karhemere Bin Shamamba ◽  
Pitchou Bitshi ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Genomic Sequence ◽  
Democratic Republic Of Congo ◽  
Coding Region ◽  
Reading Frame ◽  
Immunodeficiency Virus ◽  
Primate Lentiviruses ◽  
Infected Cells ◽  
Mona Monkey ◽  
Hiv 1

ABSTRACT We report the identification of a new simian immunodeficiency virus (SIV), designated SIVden, in a naturally infected Dent's Mona monkey (Cercopithecus mona denti), which was kept as pet in Kinshasa, capital of the Democratic Republic of Congo. SIVden is genetically distinct from the previously characterized primate lentiviruses. Analysis of the full-length genomic sequence revealed the presence of a vpu open reading frame. This gene is also found in the virus lineage of human immunodeficiency virus type 1 (HIV-1) and chimpanzee immunodeficiency virus (SIVcpz) and was recently described in viruses isolated from Cercopithecus nictitans, Cercopithecus mona, and Cercopithecus cephus. The SIVden vpu coding region is shorter than the HIV-1/SIVcpz and the SIVgsn, SIVmon, and SIVmus counterparts. Unlike Pan troglodytes schweinfurthii viruses (SIVcpzPts) and Cercopithecus monkey viruses (SIVgsn, SIVmon, and SIVmus), the SIVden Vpu contains the characteristic DSGXES motif which was shown to be involved in Vpu-mediated CD4 and IκBα proteolysis in HIV-1 infected cells. Although it harbors a vpu gene, SIVden is phylogenetically closer to SIVdeb isolated from De Brazza's monkeys (Cercopithecus neglectus), which lacks a vpu gene, than to Cercopithecus monkey viruses, which harbor a vpu sequence.

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 Differential Restriction of Human Immunodeficiency Virus Type 2 and Simian Immunodeficiency Virus SIVmac by TRIM5α Alleles

2005 ◽  
Vol 79 (18) ◽  
pp. 11580-11587 ◽  
Author(s):  
Laura M. J. Ylinen ◽  
Zuzana Keckesova ◽  
Sam J. Wilson ◽  
Srinika Ranasinghe ◽  
Greg J. Towers
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Squirrel Monkey ◽  
New World ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Sooty Mangabey ◽  
Immunodeficiency Virus ◽  
Primate Lentiviruses ◽  
Hiv 1

ABSTRACT Primate lentiviruses have narrow host ranges, due in part to their sensitivities to mammalian intracellular antiviral factors such as APOBEC3G and TRIM5α. Despite the protection provided by this innate immune system, retroviruses are able to transfer between species where they can cause disease. This is true for sooty mangabey simian immunodeficiency virus, which has transferred to humans as HIV-2 and to rhesus macaques as SIVmac, where it causes AIDS. Here we examine the sensitivities of the closely related HIV-2 and SIVmac to restriction by TRIM5α. We show that rhesus TRIM5α can restrict HIV-2 but not the closely related SIVmac. SIVmac has not completely escaped TRIM5α, as shown by its sensitivity to distantly related TRIM5α from the New World squirrel monkey. Squirrel monkey TRIM5α blocks SIVmac infection after DNA synthesis and is not saturable with restriction-sensitive virus-like particles. We map the determinant for TRIM5α sensitivity to the structure in the capsid protein that recruits CypA into HIV-1 virions. We also make an SIV, mutated at this site, which bypasses restriction in all cells tested.

scholarly journals Simian Immunodeficiency Virus SIVmac239, but Not SIVmac316, Binds and Utilizes Human CD4 More Efficiently than Rhesus CD4

2017 ◽  
Vol 91 (18) ◽  
Author(s):  
Christoph H. Fellinger ◽  
Matthew R. Gardner ◽  
Charles C. Bailey ◽  
Michael Farzan
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Human Case ◽  
Human Infection ◽  
Sooty Mangabey ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

ABSTRACT Rhesus macaques are used to model human immunodeficiency virus type 1 (HIV-1) infections, but they are not natural hosts of HIV-1 or any simian immunodeficiency virus (SIV). Rather, they became infected with SIV through cross-species transfer from sooty mangabeys in captivity. It has been shown that HIV-1 utilizes rhesus CD4 less efficiently than human CD4. However, the relative ability of SIV envelope glycoproteins to bind or utilize these CD4 orthologs has not been reported. Here we show that several SIV isolates, including SIVmac239, are more efficiently neutralized by human CD4-Ig (huCD4-Ig) than by the same molecule bearing rhesus CD4 domains 1 and 2 (rhCD4-Ig). An I39N mutation in CD4 domain 1, present in human and sooty mangabey CD4 orthologs, largely restored rhCD4-Ig neutralization of SIVmac239 and other SIV isolates. We further observed that SIVmac316, a derivative of SIVmac239, bound to and was neutralized by huCD4-Ig and rhCD4-Ig with nearly identical efficiencies. Introduction of two SIVmac316 CD4-binding site residues (G382R and H442Y) into the SIVmac239 envelope glycoprotein (Env) markedly increased its neutralization sensitivity to rhesus CD4-Ig without altering neutralization by human CD4-Ig, SIV neutralizing antibodies, or sera from SIV-infected macaques. These changes also allowed SIVmac239 Env to bind rhCD4-Ig more efficiently than huCD4-Ig. The variant with G382R and H442Y (G382R/H442Y variant) also infected cells expressing rhesus CD4 with markedly greater efficiency than did unaltered SIVmac239 Env. We propose that infections of rhesus macaques with SIVmac239 G382R/H442Y might better model some aspects of human infections. IMPORTANCE Rhesus macaque infection with simian immunodeficiency virus (SIV) has served as an important model of human HIV-1 infection. However, differences between this model and the human case have complicated the development of vaccines and therapies. Here we report the surprising observation that SIVmac239, a commonly used model virus, more efficiently utilizes human CD4 than the CD4 of rhesus macaques, whereas the closely related virus SIVmac316 uses both CD4 orthologs equally well. We used this insight to generate a form of SIVmac239 envelope glycoprotein (Env) that utilized rhesus CD4 more efficiently, while retaining its resistance to antibodies and sera from infected macaques. This Env can be used to make the rhesus model more similar in some ways to human infection, for example by facilitating infection of cells with low levels of CD4. This property may be especially important to efforts to eradicate latently infected cells.

scholarly journals Rapid Viral Decay in Simian Immunodeficiency Virus-Infected Macaques Receiving Quadruple Antiretroviral Therapy

2006 ◽  
Vol 80 (19) ◽  
pp. 9861-9864 ◽  
Author(s):  
Eleonor Brandin ◽  
Rigmor Thorstensson ◽  
Sebastian Bonhoeffer ◽  
Jan Albert
Keyword(s):  
Antiretroviral Therapy ◽  
Simian Immunodeficiency Virus ◽  
Piecewise Linear ◽  
Linear Regression Analysis ◽  
Plasma Virus ◽  
Days Of Therapy ◽  
Immunodeficiency Virus ◽  
Plasma Virus Load ◽  
Primate Lentiviruses ◽  
Hiv 1

ABSTRACT The viral dynamics in human immunodeficiency virus type 1 (HIV-1) infection have been studied extensively using mathematical modeling, but data from other primate lentivirus systems are scarce. This study was initiated to increase the understanding of the differences and similarities between the different primate lentiviruses. Four cynomolgus macaques were infected with SIVmac251. Six months after infection the monkeys received a 7-day course of subcutaneous, quadruple antiretroviral therapy with zidovudine, lamivudine, tenofovir, and ritonavir-boosted lopinavir. Plasma virus levels were determined before therapy, daily during the first 10 days of therapy, and after 14 days using a sensitive commercial reverse transcriptase assay. All four monkeys showed a rapid and uniform decline in plasma virus load between day 1 and day 4 of treatment (first-phase decay). Two mathematical models, a piecewise linear regression analysis and a nonlinear model, were used to estimate the rate of viral decay in plasma and gave similar results. The mean half-life for plasma virus was 0.47 days (range, 0.37 to 0.50) and reflects the underlying decline of virus-producing CD4+ lymphocytes. This is the fastest primate lentivirus decay described hitherto. The rapid decay may be due to the high antiviral potency of the therapy or to intrinsic differences between simian immunodeficiency virus (SIV) infection in macaques and HIV-1 infection in humans.

scholarly journals Rapid Clearance of Simian Immunodeficiency Virus Particles from Plasma of Rhesus Macaques

1999 ◽  
Vol 73 (1) ◽  
pp. 855-860 ◽  
Author(s):  
Linqi Zhang ◽  
Peter J. Dailey ◽  
Tian He ◽  
Agegnehu Gettie ◽  
Sebastian Bonhoeffer ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Burst Size ◽  
Accurate Estimate ◽  
Short Period ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Rapid Clearance ◽  
Hiv 1

ABSTRACT Perturbation of the equilibrium between human immunodeficiency virus type 1 (HIV-1) and the infected host by administering antiretroviral agents has revealed the rapid turnover of both viral particles and productively infected cells. In this study, we used the infusion of simian immunodeficiency virus (SIV) particles into rhesus macaques to obtain a more accurate estimate of viral clearance in vivo. Consistently, exogenously infused virions were cleared from plasma with an extremely short half-life, on the order of minutes (a mean of 3.3 min). This new estimate is ∼100-fold lower than the upper bound of 6 h previously reported for HIV-1 in infected humans. In select animals, multiple tissues were collected at the completion of each experiment to track the potential sites of virion clearance. Detectable levels of SIV RNA were found in lymph nodes, spleen, lungs, and liver, but not in other tissues examined. However, only ∼1 to 10% or less of the infused virions were accounted for by the thorough tissue sampling, indicating that the vast majority of the infused particles must have been degraded over a short period of time. Should the rapid clearance of virions described here be applicable to infected patients, then HIV-1 production and thus the number of productively infected CD4+ T lymphocytes or the viral burst size must be proportionally higher than previous minimal estimates.

scholarly journals Simian Immunodeficiency Virus in Which nef and U3 Sequences Do Not Overlap Replicates Efficiently In Vitro and In Vivo in Rhesus Macaques

2001 ◽  
Vol 75 (17) ◽  
pp. 8137-8146 ◽  
Author(s):  
Jan Münch ◽  
Nadia Adam ◽  
Nathaly Finze ◽  
Nicole Stolte ◽  
Christiane Stahl-Hennig ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Point Mutations ◽  
Regulatory Elements ◽  
Coding Sequences ◽  
Reading Frame ◽  
Immunodeficiency Virus ◽  
Primate Lentiviruses

ABSTRACT The nef genes of human immunodeficiency virus and simian immunodeficiency virus (SIV) overlap about 80% of the U3 region of the 3′ long terminal repeat (LTR) and contain several essentialcis-acting elements (here referred to as the TPI region): a T-rich region, the polypurine tract, and attachment (att) sequences required for integration. We inactivated the TPI region in the nef reading frame of the pathogenic SIVmac239 clone (239wt) by 13 silent point mutations. To restore viral infectivity, intact cis-regulatory elements were inserted just downstream of the mutatednef gene. The resulting SIV genome contains U3 regions that are 384 bp shorter than the 517-bp 239wt U3 region. Overall, elimination of the duplicated Nef coding sequences truncates the proviral genome by 350 bp. Nonetheless, it contains all known coding sequences and cis-acting elements. The TPI mutant virus expressed functional Nef and replicated like 239wt in all cell culture assays and in vivo in rhesus macaques. Notably, these SIVmac constructs allow us to study Nef function in the context of replication-competent viruses without the restrictions of overlapping LTR sequences and important cis-acting elements. The genomes of all known primate lentiviruses contain a large overlap between nefand the U3 region. We demonstrate that this conserved genomic organization is not obligatory for efficient viral replication and pathogenicity.

scholarly journals Envelope Glycoprotein Internalization Protects Human and Simian Immunodeficiency Virus-Infected Cells from Antibody-Dependent Cell-Mediated Cytotoxicity

2015 ◽  
Vol 89 (20) ◽  
pp. 10648-10655 ◽  
Author(s):  
Benjamin von Bredow ◽  
Juan F. Arias ◽  
Lisa N. Heyer ◽  
Matthew R. Gardner ◽  
Michael Farzan ◽  
...  
Keyword(s):  
Cell Surface ◽  
Simian Immunodeficiency Virus ◽  
Virus Assembly ◽  
Antibody Responses ◽  
Antiretroviral Therapies ◽  
Cytoplasmic Tails ◽  
Immunodeficiency Virus ◽  
Dependent Cell ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTThe cytoplasmic tails of human and simian immunodeficiency virus (HIV and SIV, respectively) envelope glycoproteins contain a highly conserved, membrane-proximal endocytosis motif that prevents the accumulation of Env on the surface of infected cells prior to virus assembly. Using an assay designed to measure the killing of virus-infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC), we show that substitutions in this motif increase the susceptibility of HIV-1- and SIV-infected cells to ADCC in a manner that directly correlates with elevated Env levels on the surface of virus-infected cells. In the case of HIV-1, this effect is additive with a deletion invpurecently shown to enhance the susceptibility of HIV-1-infected cells to ADCC as a result of tetherin-mediated retention of budding virions on the cell surface. These results reveal a previously unappreciated role for the membrane-proximal endocytosis motif of gp41 in protecting HIV-1- and SIV-infected cells from antibody responses by regulating the amount of Env present on the cell surface.IMPORTANCEThis study reveals an unappreciated role for the membrane-proximal endocytosis motif of gp41 in protecting HIV-1- and SIV-infected cells from elimination by Env-specific antibodies. Thus, strategies designed to interfere with this mechanism of Env internalization may improve the efficacy of antibody-based vaccines and antiretroviral therapies designed to enhance the immunological control of HIV-1 replication in chronically infected individuals.

scholarly journals Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques.

1996 ◽  
Vol 183 (1) ◽  
pp. 215-225 ◽  
Author(s):  
A I Spira ◽  
P A Marx ◽  
B K Patterson ◽  
J Mahoney ◽  
R A Koup ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Sexual Transmission ◽  
Mucosal Transmission ◽  
Cellular Targets ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Internal Iliac ◽  
Infected Cells ◽  
Hiv 1

We used the simian immunodeficiency virus (SIV)/rhesus macaque model to study events that underlie sexual transmission of human immunodeficiency virus type 1 (HIV-1). Four female rhesus macaques were inoculated intravaginally with SIVmac251, and then killed 2, 5, 7, and 9 d later. A technique that detected polymerase chain reaction-amplified SIV in situ showed that the first cellular targets for SIV were in the lamina propria of the cervicovaginal mucosa, immediately subjacent to the epithelium. Phenotypic and localization studies demonstrated that many of the infected cells were likely to be dendritic cells. Within 2 d of inoculation, infected cells were identified in the paracortex and subcapsular sinus of the draining internal iliac lymph nodes. Subsequently, systemic dissemination of SIV was rapid, since culturable virus was detectable in the blood by day 5. From these results, we present a model for mucosal transmission of SIV and HIV-1.

scholarly journals Vaccination of Macaques with DNA Followed by Adenoviral Vectors Encoding Simian Immunodeficiency Virus (SIV) Gag Alone Delays Infection by Repeated Mucosal Challenge with SIV

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Neil Almond ◽  
Neil Berry ◽  
Richard Stebbings ◽  
Mark Preston ◽  
Claire Ham ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
T Cell Responses ◽  
Virus Load ◽  
Macaque Model ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Hiv 1

ABSTRACT Vaccines aimed at inducing T cell responses to protect against human immunodeficiency virus (HIV) infection have been under development for more than 15 years. Replication-defective adenovirus (rAd) vaccine vectors are at the forefront of this work and have been tested extensively in the simian immunodeficiency virus (SIV) challenge macaque model. Vaccination with rAd vectors coding for SIV Gag or other nonenvelope proteins induces T cell responses that control virus load but disappointingly is unsuccessful so far in preventing infection, and attention has turned to inducing antibodies to the envelope. However, here we report that Mauritian cynomolgus macaques (MCM), Macaca fascicularis, vaccinated with unmodified SIV gag alone in a DNA prime followed by an rAd boost exhibit increased protection from infection by repeated intrarectal challenge with low-dose SIVmac251. There was no evidence of infection followed by eradication. A significant correlation was observed between cytokine expression by CD4 T cells and delayed infection. Vaccination with gag fused to the ubiquitin gene or fragmented, designed to increase CD8 magnitude and breadth, did not confer resistance to challenge or enhance immunity. On infection, a significant reduction in peak virus load was observed in all vaccinated animals, including those vaccinated with modified gag. These findings suggest that a nonpersistent viral vector vaccine coding for internal virus proteins may be able to protect against HIV type 1 (HIV-1) infection. The mechanisms are probably distinct from those of antibody-mediated virus neutralization or cytotoxic CD8 cell killing of virus-infected cells and may be mediated in part by CD4 T cells. IMPORTANCE The simian immunodeficiency virus (SIV) macaque model represents the best animal model for testing new human immunodeficiency virus type 1 (HIV-1) vaccines. Previous studies employing replication-defective adenovirus (rAd) vectors that transiently express SIV internal proteins induced T cell responses that controlled virus load but did not protect against virus challenge. However, we show for the first time that SIV gag delivered in a DNA prime followed by a boost with an rAd vector confers resistance to SIV intrarectal challenge. Other partially successful SIV/HIV-1 protective vaccines induce antibody to the envelope and neutralize the virus or mediate antibody-dependent cytotoxicity. Induction of CD8 T cells which do not prevent initial infection but eradicate infected cells before infection becomes established has also shown some success. In contrast, the vaccine described here mediates resistance by a different mechanism from that described above, which may reflect CD4 T cell activity. This could indicate an alternative approach for HIV-1 vaccine development.

scholarly journals Characterization of a Novel Simian Immunodeficiency Virus (SIVmonNG1) Genome Sequence from a Mona Monkey (Cercopithecus mona)

2003 ◽  
Vol 77 (12) ◽  
pp. 6879-6888 ◽  
Author(s):  
Katrina L. Barlow ◽  
Adebowale Oluwafemi Ajao ◽  
Jonathan P. Clewley
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Gene Sequence ◽  
Pcr Primers ◽  
Open Reading Frames ◽  
Primate Species ◽  
Immunodeficiency Virus ◽  
Mona Monkey ◽  
Hiv 1

ABSTRACT A novel simian immunodeficiency virus (SIV) sequence has been recovered from RNA extracted from the serum of a mona monkey (Cercopithecus mona) wild born in Nigeria. The sequence was obtained by using novel generic (degenerate) PCR primers and spans from two-thirds into the gag gene to the 3′ poly(A) tail of the SIVmonNG1 RNA genome. Analysis of the open reading frames revealed that the SIVmonNG1 genome codes for a Vpu protein, in addition to Gag, Pol, Vif, Vpr, Tat, Rev, Env, and Nef proteins. Previously, only lentiviruses infecting humans (human immunodeficiency virus type 1 [HIV-1]) and chimpanzees (SIVcpz) were known to have a vpu gene; more recently, this has also been found in SIVgsn from Cercopithecus nictitans. Overall, SIVmonNG1 most closely resembles SIVgsn: the env gene sequence groups with HIV-1/SIVcpz env sequences, whereas the pol gene sequence clusters closely with the pol sequence of SIVsyk from Cercopithecus albogaris. By bootscanning and similarity plotting, the first half of pol resembles SIVsyk, whereas the latter part is closer to SIVcol from Colobus guereza. The similarities between the complex mosaic genomes of SIVmonNG1 and SIVgsn are consistent with a shared or common lineage. These data further highlight the intricate nature of the relationships between the SIVs from different primate species and will be helpful for unraveling these associations.

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