Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Plaeger, Susan; Collins, Brenda S.; Musib, Runa; Deeks, Steven G.; Read, Sarah; Embry, Alan C.

doi:10.1089/aid.2011.0213

Cited by 61 publications

(46 citation statements)

References 61 publications

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“…Signaling due to extracellular DNA could potentially represent an additional pathway to chronic immune activation commonly seen in HIV-1-infected individuals (57). An additional study examining the levels of plasma DNA in patients on antiretroviral therapy would also be informative, as chronic activation is present, albeit at a lower level, in patients on long-term therapy and is associated with decreased longevity, cardiovascular disease, and metabolic syndrome (58).…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) ProvirusesIn Vivobut Not to Increased Virion Production

Bhardwaj

Maldarelli

Mellors

et al. 2014

J Virol

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Recent studies suggest that human endogenous retrovirus group K (HERV-K) provirus expression plays a role in the pathogenesis of HIV-1 infection. In particular, RNA from the HML-2 subgroup of HERV-K proviruses has been reported to be highly expressed at the cellular level and detectable in the plasma of HIV-1-infected patients, suggestive of virion production and, perhaps, replication. In this study, we developed an HML-2-specific quantitative-PCR assay that detects 51 of the 89 known HML-2 proviruses in the human genome. Plasma and peripheral blood mononuclear cells (PBMCs) from HIV-negative controls and HIV-1-infected patients were collected for analysis of HML-2 RNA expression. Contrary to previous reports, we did not detect high levels of HML-2 RNA in the plasma of HIV-1-infected patients, but we did observe a significant increase of HML-2 RNA in total PBMCs compared to HIV-negative controls. The level of HML-2 expression in PBMCs does not appear to be related to patient use of antiretrovirals or to HIV-1 plasma RNA, cellular RNA, or cellular DNA levels. To investigate the source of HML-2 RNA expression, patient PBMCs were sorted into CD3 ؉ CD4 ؉ , CD3 ؉ CD8 ؉ , CD3 ؊ CD14 ؉ , and CD3 ؊ CD20 ؉ cell subsets and then analyzed for HML-2 RNA levels. No single cell subset was enriched for HML-2 RNA expression in HIV-1-infected patients, but there appears to be substantial variability in the level of HML-2 expression depending on the cell type. IMPORTANCEHere, we report that human endogenous retrovirus group K (HERV-K) (HML-2) proviruses are expressed at significantly higher levels in peripheral blood mononuclear cells (PBMCs) from patients with HIV-1 infection than in those from uninfected individuals. However, contrary to previous reports, this expression did not lead to detectable virions in the plasma of these patients. In addition, we found that HML-2 proviruses were expressed in multiple blood cell types from HIV-1-infected individuals, and the magnitude of HML-2 expression was not related to HIV-1 disease markers in this patient cohort. These findings may have implications for HML-2-based therapies targeting HIV-1 infection.

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Section: Discussionmentioning

confidence: 99%

HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) ProvirusesIn Vivobut Not to Increased Virion Production

Bhardwaj

Maldarelli

Mellors

et al. 2014

J Virol

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“…Further SMART data identified higher rates of cardiovascular, renal, and hepatic disease in the interrupted-treatment group [17]. Proposed mechanisms between chronic inflammation and the greater risk for specific age-associated diseases observed in HIV infection have been reviewed in detail elsewhere [14,[18][19][20].…”

Section: Inflammagingmentioning

confidence: 99%

Biologic aging, frailty, and age-related disease in chronic HIV infection

Brothers

Rockwood

2014

Current Opinion in HIV and AIDS

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“…37 It is interesting that there were inverse correlations between immune activation and SIV-target cell restoration, suggesting that reduction of immune activation benefits the reconstitution of T cells (Fig. 6E and 6F).…”

Section: Impact Of Art On Siv-infected Chinese Macaquesmentioning

confidence: 92%

Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques of Simian Immunodeficiency Virus Infection

Ling

Rogers²,

Johnson³

et al. 2013

AIDS Research and Human Retroviruses

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Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (< 30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to < 30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5 + CD4 + mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to < 30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.

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Immune Activation in the Pathogenesis of Treated Chronic HIV Disease: A Workshop Summary

Cited by 61 publications

References 61 publications

HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) ProvirusesIn Vivobut Not to Increased Virion Production

HIV-1 Infection Leads to Increased Transcription of Human Endogenous Retrovirus HERV-K (HML-2) ProvirusesIn Vivobut Not to Increased Virion Production

Biologic aging, frailty, and age-related disease in chronic HIV infection

Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques of Simian Immunodeficiency Virus Infection

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