Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection

Jobe, Ousman; Ariyoshi, Koya; Marchant, Arnaud; Sabally, S; Corrah, Tumani; Berry, Neil; Jaffar, Shabbar; Whittle, Hilton

doi:10.1046/j.1365-2249.1999.00914.x

Cited by 13 publications

(8 citation statements)

References 22 publications

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“…There are no data available on lymphoid tissues during HIV-2 disease. Of note, the establishment of HIV-2 infection is associated with levels of proviral DNA similar to those found in HIV-1, suggesting an equivalent viral dissemination despite the reduced HIV-2 viremia [26]–[29],[72]. Therefore, it is plausible that HIV-2 RNA and/or HIV-2 proteins may induce pDC maturation and migration.…”

Section: Discussionmentioning

confidence: 84%

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

et al. 2009

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Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-α production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of “attenuated” HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-α production does occur.

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Section: Discussionmentioning

confidence: 84%

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

et al. 2009

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“…Levels of proviral DNA are similar in both infections (although there may be differences in proviral DNA levels between HIV‐1 and HIV‐2 if more sophisticated analytical methods are used ), and viral RNA is usually undetectable in aviraemic HIV‐2‐infected subjects, despite demonstrable proviral DNA . Within cohorts, variations in proviral DNA correlate with plasma viral load (and rates of CD4 decline) for both infections but the relationship between proviral DNA and circulating viral RNA is quite different for the two viruses . Interestingly, proviral load in peripheral blood cells correlates closely with that in lymph node lymphocytes suggesting that infected cells circulate freely between nodes and blood .…”

Section: Lessons From Survival and Mortality And Predictors Of Survimentioning

confidence: 98%

Comparing HIV‐1 and HIV‐2 infection: Lessons for viral immunopathogenesis

Nyamweya

Hegedus

Jaye

et al. 2013

Reviews in Medical Virology

189

139

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HIV-1 and HIV-2 share many similarities including their basic gene arrangement, modes of transmission, intracellular replication pathways and clinical consequences: both result in AIDS. However, HIV-2 is characterised by lower transmissibility and reduced likelihood of progression to AIDS. The underlying mechanistic differences between these two infections illuminate broader issues of retroviral pathogenesis, which remain incompletely understood. Comparisons between these two infections from epidemiological, clinical, virologic and immunologic viewpoints provide a basis for hypothesis generation and testing in this 'natural experiment' in viral pathogenesis. In terms of epidemiology, HIV-2 remains largely confined to West Africa, whereas HIV-1 extends worldwide. Clinically, HIV-2 infected individuals seem to dichotomise, most remaining long-term non-progressors, whereas most HIV-1 infected individuals progress. When clinical progression occurs, both diseases demonstrate very similar pathological processes, although progression in HIV-2 occurs at higher CD4 counts. Plasma viral loads are consistently lower in HIV-2, as are average levels of immune activation. Significant differences exist between the two infections in all components of the immune system. For example, cellular responses to HIV-2 tend to be more polyfunctional and produce more IL-2; humoral responses appear broader with lower magnitude intratype neutralisation responses; innate responses appear more robust, possibly through differential effects of tripartite motif protein isoform 5 alpha. Overall, the immune response to HIV-2 appears more protective against disease progression suggesting that pivotal immune factors limit viral pathology. If such immune responses could be replicated or induced in HIV-1 infected patients, they might extend survival and reduce requirements for antiretroviral therapy.

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“…If the RNA viral loads in HIV-1 and HIV-2 infections differ significantly, the proviral loads in the peripheral blood are similar (5,20), and they are approximately five times higher in lymph nodes for both infections (14). Thus, a number of circulating CD4 T cells in infected individuals carry the HIV-2 provirus and may express the nef gene independently of the functionality of the other viral genes.…”

Section: Vol 83 2009 Hiv-2 Nef Does Not Protect Against Disease Promentioning

confidence: 99%

Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

Feldmann

Leligdowicz

Jaye

et al. 2009

J Virol

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Chronic immune activation is thought to play a major role in human immunodeficiency virus (HIV) pathogenesis, but the relative contributions of multiple factors to immune activation are not known. One proposed mechanism to protect against immune activation is the ability of Nef proteins from some HIV and simian immunodeficiency virus strains to downregulate the T-cell receptor (TCR)-CD3 complex of the infected cell, thereby reducing the potential for deleterious activation. HIV type 1 (HIV-1) Nef has lost this property. In contrast to HIV-1, HIV-2 infection is characterized by a marked disparity in the disease course, with most individuals maintaining a normal life span. In this study, we examined the relationship between the ability of HIV-2 Nef proteins to downregulate the TCR and immune activation, comparing progressors and nonprogressors. Representative Nef variants were isolated from 28 HIV-2-infected individuals. We assessed their abilities to downregulate the TCR from the surfaces of CD4 T cells. In the same individuals, the activation of peripheral lymphocytes was evaluated by measurement of the expression levels of HLA-DR and CD38. We observed a striking correlation of the TCR downregulation efficiency of HIV-2 Nef variants with immune activation in individuals with a low viral load. This strongly suggests that Nef expression can influence the activation state of the immune systems of infected individuals. However, the efficiency of TCR downregulation by Nef was not reduced in progressing individuals, showing that TCR downregulation does not protect against progression in HIV-2 infection.

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Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection

Cited by 13 publications

References 22 publications

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

Comparing HIV‐1 and HIV‐2 infection: Lessons for viral immunopathogenesis

Downregulation of the T-Cell Receptor by Human Immunodeficiency Virus Type 2 Nef Does Not Protect against Disease Progression

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