Changes in simian immunodeficiency virus reverse transcriptase alleles that appear during infection of macaques enhance infectivity and replication in CD4+ T cells

Biesinger, Tasha; Kimata, Monica T. Yu; Kimata, Jason T.

doi:10.1016/j.virol.2007.08.011

Cited by 6 publications

(9 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PBMC were isolated from heparinized rhesus, pig-tail, or human peripheral blood by Ficoll gradient centrifugation and activated by costimulation with anti-CD3/anti-CD28 monoclonal antibodies and interleukin-2 as previously described (7,9,46). At 3 days after costimulation the cells were Ͼ98% CD3 ϩ T cells, as indicated by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Vif Substitution Enables Persistent Infection of Pig-Tailed Macaques by Human Immunodeficiency Virus Type 1

Thippeshappa

Polacino

Kimata

et al. 2011

J Virol

Self Cite

View full text Add to dashboard Cite

Among Old World monkeys, pig-tailed macaques (Pt) are uniquely susceptible to human immunodeficiency virus type 1 (HIV-1), although the infection does not persist. We demonstrate that the susceptibility of Pt T cells to HIV-1 infection is due to the absence of postentry inhibition by a TRIM5 isoform. Notably, substitution of the viral infectivity factor protein, Vif, with that from pathogenic SIVmne enabled replication of HIV-1 in Pt T cells in vitro. When inoculated into juvenile pig-tailed macaques, the Pt-tropic HIV-1 persistently replicated for more than 1.5 to 2 years, producing low but measurable plasma viral loads and persistent proviral DNA in peripheral blood mononuclear cells. It also elicited strong antibody responses. However, there was no decline in CD4؉ T cells or evidence of disease. Surprisingly, the Pt-tropic HIV-1 was rapidly controlled when inoculated into newborn Pt macaques, although it transiently rebounded after 6 months. We identified two notable differences between the Pt-tropic HIV-1 and SIVmne. First, SIV Vif does not associate with Pt-tropic HIV-1 viral particles. Second, while Pt-tropic HIV-1 degrades both Pt APOBEC3G and APOBEC3F, it prevents their inclusion in virions to a lesser extent than pathogenic SIVmne. Thus, while SIV Vif is necessary for persistent infection by Pt-tropic HIV-1, improved expression and inhibition of APOBEC3 proteins may be required for robust viral replication in vivo. Additional adaptation of the virus may also be necessary to enhance viral replication. Nevertheless, our data suggest the potential for the pig-tailed macaque to be developed as an animal model of HIV-1 infection and disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Vif Substitution Enables Persistent Infection of Pig-Tailed Macaques by Human Immunodeficiency Virus Type 1

Thippeshappa

Polacino

Kimata

et al. 2011

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…macrophages, resting T cells, activated T cells) have variable dNTP pools (Traut, 1994;Diamond et al 2004;Hauschka, 1973;Fuller et al 1982;Skoog and Bjursell, 1974;Yao et al 2003). A recent study with SIV RT variants isolated from infected macaques demonstrated rapid selection against an RT variant with higher replication fi delity (Biesinger et al 2008). These data suggest that RT's ability to misincorporate dNTPs in settings with limited resource availability or the indirect effect misincorporation has on processivity allows for more rapid genomic reverse transcription and integration and is an important aspect of replication fi tness.…”

Section: Viral Determinants Altering Phenotypementioning

confidence: 99%

HIV-1 Transmission, Replication Fitness and Disease Progression

Biesinger

Kimata

2008

Virology�(Auckl)

Self Cite

View full text Add to dashboard Cite

Upon transmission, human immunodefi ciency virus type 1 (HIV-1) establishes infection of the lymphatic reservoir, leading to profound depletion of the memory CD4+ T cell population despite the induction of the adaptive immune response. The rapid evolution and association of viral variants having distinct characteristics during different stages of infection, the level of viral burden, and rate of disease progression suggest a role for viral variants in this process. Here, we review the literature on HIV-1 variants and disease and discuss the importance of viral fi tness for transmission and disease.

show abstract

“…9 Indeed, our studies with the SIV-macaque model demonstrated that the appearance of variants with greater replicative capacity in CD4+ T-cells influenced plasma viral load and the rate of disease progression. 29 Importantly, highly pathogenic variants also show greater replicative capacity in DC-T-cell cocultures compared to the minimally pathogenic parental virus 26, 30 , suggesting that SIV, and by extension HIV-1, evolve during infection to exploit DC-T-cell interactions for viral replication. The data presented here support this hypothesis and show a direct relationship between plasma viral RNA levels in the host and infectivity and replication capacity of the infecting viruses in DC-T-cell cocultures.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cell–Mediated HIV-1 Infection of T Cells Demonstrates a Direct Relationship to Plasma Viral RNA Levels

Arora

Bull

Siwak

et al. 2010

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

Objective To examine the relationship between infectivity of HIV-1 variants in dendritic cell-mediated in trans infection of T-cells and plasma viral RNA levels in infected subjects. Methods HIV-1 was isolated from PBMCs of chronically infected individuals, typed for coreceptor usage, and viral replication was examined in monocyte derived-dendritic cells-peripheral blood lymphocytes (DC-PBL) co-cultures. The rate of p24 antigen production during the logarithmic phase of viral replication was determined by ELISA. Additionally, nef variants were cloned and expressed in trans with a HIV-luciferase vector and CCR5-tropic HIV-1 envelope, and infectivity was measured in DC-mediated capture-transfer assays. Results Replication capacity of HIV-1 viral CCR5-tropic isolates in DC-PBL co-cultures was linearly associated with the plasma viral RNA levels in a cohort of HIV-1 infected individuals exhibiting an inverse relationship between plasma viral RNA and CD4 cell count. Furthermore, infectivity activity of Nef variants in context of DC-mediated enhanced infection of T-cells also showed a linear relationship to plasma viral RNA levels. Conclusion These results illustrate that replication capacity of HIV-1 in DC-T-cell cultures is a significant predictor of plasma viral RNA level. The data suggest that adaptation of HIV-1 to DC interactions with T-cells influences the level of viral replication in the host.

show abstract

Changes in simian immunodeficiency virus reverse transcriptase alleles that appear during infection of macaques enhance infectivity and replication in CD4+ T cells

Cited by 6 publications

References 47 publications

Vif Substitution Enables Persistent Infection of Pig-Tailed Macaques by Human Immunodeficiency Virus Type 1

Vif Substitution Enables Persistent Infection of Pig-Tailed Macaques by Human Immunodeficiency Virus Type 1

HIV-1 Transmission, Replication Fitness and Disease Progression

Dendritic Cell–Mediated HIV-1 Infection of T Cells Demonstrates a Direct Relationship to Plasma Viral RNA Levels

Contact Info

Product

Resources

About