Immunogenicity and protective efficacy of Gag/Pol/Env vaccines derived from temporal isolates of SIVmne against cognate virus challenge

Polacino, Patricia; Cleveland, Brad; Zhu, Yong-de; Kimata, Jason T.; Overbaugh, Julie; Anderson, David; Hu, Shiu Lok

doi:10.1111/j.1600-0684.2007.00243.x

Cited by 26 publications

(34 citation statements)

References 56 publications

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“…Intravenous inoculation with 9500 TCID50 SHIV-1157ipd3N4 (provided by Ruth Ruprecht, Texas Biomedical Research Institute), administration of cART (tenofovir [PMPA], emtricitabine [FTC], and raltegravir), and measurement of plasma VLs and absolute CD4 + and CD8 + T cell counts were conducted as described previously (11,14,58). PMPA and FTC were gifts of Gilead Sciences, and raltegravir was a gift of Merck.…”

Section: Methodsmentioning

confidence: 99%

Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

Peterson¹,

Benne²,

Polacino³

et al. 2017

JCI Insight

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Section: Methodsmentioning

confidence: 99%

Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

Peterson¹,

Benne²,

Polacino³

et al. 2017

JCI Insight

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“…HIV-1-specific antibodies were measured by ELISA as previously described, except that gradient-purified and disrupted whole HIV-1 virions were used as the capture antigen (34,68).…”

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

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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.

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“…Plasma viral load was determined by realtime reverse transcription (RT)-quantitative PCR (qPCR) based on published methods (21). The intracellular viral RNA load in the rectal mucosa was quantified as previously described (22). mRNA library preparation.…”

Section: Methodsmentioning

confidence: 99%

Deep Transcriptional Sequencing of Mucosal Challenge Compartment from Rhesus Macaques Acutely Infected with Simian Immunodeficiency Virus Implicates Loss of Cell Adhesion Preceding Immune Activation

Barrenäs

Palermo

Agricola

et al. 2014

J Virol

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Pathology resulting from human immunodeficiency virus (HIV) infection is driven by protracted inflammation; the primary loss of CD4؉ T cells is caused by activation-driven apoptosis. Recent studies of nonhuman primates (NHPs) have suggested that during the acute phase of infection, antiviral mucosal immunity restricts viral replication in the primary infection compartment. These studies imply that HIV achieves systemic infection as a consequence of a failure in host antiviral immunity. Here, we used high-dose intrarectal inoculation of rhesus macaques with simian immunodeficiency virus (SIV) SIV mac251 to examine how the mucosal immune system is overcome by SIV during acute infection. The host response in rectal mucosa was characterized by deep mRNA sequencing (mRNA-seq) at 3 and 12 days postinoculation (dpi) in 4 animals for each time point. While we observed a strong host transcriptional response at 3 dpi, functions relating to antiviral immunity were absent. Instead, we observed a significant number of differentially expressed genes relating to cell adhesion and reorganization of the cytoskeleton. We also observed downregulation of genes encoding members of the claudin family of cell adhesion molecules, which are coexpressed with genes associated with pathology in the colorectal mucosa, and a large number of noncoding transcripts. In contrast, at 12 dpi the differentially expressed genes were enriched in those involved with immune system functions, in particular, functions relating to T cells, B cells, and NK cells. Our findings indicate that host responses that negatively affect mucosal integrity occur before inflammation. Consequently, when inflammation is activated at peak viremia, mucosal integrity is already compromised, potentially enabling rapid tissue damage, driving further inflammation. IMPORTANCEThe HIV pandemic is one of the major threats to human health, causing over a million deaths per year. Recent studies have suggested that mucosal antiviral immune responses play an important role in preventing systemic infection after exposure to the virus. Yet, despite their potential role in decreasing transmission rates between individuals, these antiviral mechanisms are poorly understood. Here, we carried out the first deep mRNA sequencing analysis of mucosal host responses in the primary infection compartment during acute SIV infection. We found that during acute infection, a significant host response was mounted in the mucosa before inflammation was triggered. Our analysis indicated that the response has a detrimental effect on tissue integrity, causing increased permeability, tissue damage, and recruitment of SIV target cells. These results emphasize the importance of mucosal host responses preceding immune activation in preventing systemic SIV infection.

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Immunogenicity and protective efficacy of Gag/Pol/Env vaccines derived from temporal isolates of SIVmne against cognate virus challenge

Abstract: These results underscore the potential importance of targeting transmitted viruses through judicious choice of immunogens from early isolates for vaccine development.

Cited by 26 publications

References 56 publications

Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

Loss of immune homeostasis dictates SHIV rebound after stem-cell transplantation

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

Deep Transcriptional Sequencing of Mucosal Challenge Compartment from Rhesus Macaques Acutely Infected with Simian Immunodeficiency Virus Implicates Loss of Cell Adhesion Preceding Immune Activation

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