Low Plasma Human Immunodeficiency Virus Type 2 Viral Load Is Independent of Proviral Load: Low Virus Production In Vivo

Popper, Stephen J.; Sarr, Abdoulaye; Guèye-Ndiaye, Aı̈ssatou; Mboup, Souleymane; Essex, M.; Kanki, Phyllis J.

doi:10.1128/jvi.74.3.1554-1557.2000

Cited by 128 publications

(88 citation statements)

References 34 publications

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“…Although there are no data on the ability of IL-7 to promote HIV-2 replication, it would be expected to be comparable given the similarity of the two viral promoter regions (long terminal repeats) (59). No differences were found between the levels of HIV-2 and HIV-1 proviral DNA in PBMCs, in agreement with other studies (36,48,56). The low to undetectable HIV-2 viremia in this context further emphasizes the efficiency of the ill-defined mechanisms involved in the control of viral replication in HIV-2-infected patients in the absence of antiretroviral therapy.…”

Section: Discussionsupporting

confidence: 79%

“…Despite the distinct viremia, HIV-1-and HIV-2-infected patients have been shown to have comparable levels of cell-associated viral load as assessed by proviral DNA (36,48,49). Accordingly, we found no significant difference between the levels of PBMC proviral DNA in the HIV-1 and HIV-2 cohorts.…”

Section: No Significant Correlation Of Serum Il-7 Levels With Viremiacontrasting

confidence: 39%

“…There were no statistically significant differences between HIV-1 and HIV-2 subgroups when similar levels of CD4 depletion were compared. Statistical significance between the different HIVinfected groups as compared with healthy subjects are as follows: ‫,ء‬ p Ͻ 0.05; ‫,ءء‬ p Ͻ 0.01; and ‫,ءءء‬ p Ͻ 0.001. reduced rate of CD4 decline as expected (32,33,36,42). The graphs illustrate the consistency of the IL-7 measurements during the follow-up and document changes in serum IL-7 levels inversely related to the alterations found in CD4 T cell counts.…”

Section: The Strong Correlation Between Il-7 and Cd4 Lymphopenia Obsementioning

confidence: 90%

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Rate of Increase in Circulating IL-7 and Loss of IL-7Rα Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes

Albuquerque

Cortesão

Foxall

et al. 2007

The Journal of Immunology

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IL-7 is a nonredundant cytokine for T cell homeostasis. Circulating IL-7 levels increase in lymphopenic clinical settings, including HIV-1 infection. HIV-2 infection is considered a “natural” model of attenuated HIV disease given its much slower rate of CD4 decline than HIV-1 and limited impact on the survival of the majority of infected adults. We compared untreated HIV-1- and HIV-2-infected patients and found that the HIV-2 cohort demonstrated a delayed increase in IL-7 levels during the progressive depletion of circulating CD4 T cells as well as a dissociation between the acquisition of markers of T cell effector differentiation and the loss of IL-7Rα expression. This comparison of two persistent infections associated with progressive CD4 depletion and immune activation demonstrates that a better prognosis is not necessarily associated with higher levels of IL-7. Moreover, the delayed increase in IL-7 coupled with sustained expression of IL-7Rα suggests a maximization of available resources in HIV-2. The observation that increased IL-7 levels early in HIV-1 infection were unable to reduce the rate of CD4 loss and the impaired expression of the IL-7Rα irrespective of the state of cell differentiation raises concerns regarding the use of IL-7 therapy in HIV-1 infection.

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Section: Discussionsupporting

confidence: 79%

Section: No Significant Correlation Of Serum Il-7 Levels With Viremiacontrasting

confidence: 39%

Section: The Strong Correlation Between Il-7 and Cd4 Lymphopenia Obsementioning

confidence: 90%

See 1 more Smart Citation

Rate of Increase in Circulating IL-7 and Loss of IL-7Rα Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes

Albuquerque

Cortesão

Foxall

et al. 2007

The Journal of Immunology

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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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“…These epidemiological findings and the reduced frequency of successful virus isolation from the blood of HIV-2-infected patients (19) suggested very low levels of viremia, which was confirmed by recently developed methods to quantify HIV-2 RNA copies in the plasma (20 -22). Interestingly, quantitative assessment of HIV-2 DNA documented proviral levels similar to those observed in HIV-1-infected individuals, which was interpreted to indicate similar target cell infectivity but a decreased rate of virus production in HIV-2 infection (23,24).…”

Section: H Uman Immunodeficiency Virus Type 1 Pathogenesis Is Generalmentioning

confidence: 99%

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

Sousa

Carneiro

Meier‐Schellersheim

et al. 2002

The Journal of Immunology

438

323

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The causal relationships among CD4 cell depletion, HIV replication, and immune activation are not well understood. HIV-2 infection, “nature’s experiment” with inherently attenuated HIV disease, provides additional insights into this issue. We report the finding that in HIV-2 and HIV-1 patients with a comparable degree of CD4 depletion the imbalance in the relative sizes of the naive and memory T cell populations and the up-regulation of CD4 and CD8 cell activation markers (HLA-DR, CD38, CD69, Fas molecules) are similar, even though the viral load in the plasma of HIV-2-infected patients is two orders of magnitude lower than in HIV-1 patients and HIV-2 patients are known to have slower rates of CD4 T cell decline and a better clinical prognosis. Moreover, we found a similar increase in the frequency of cycling CD4 T cells (Ki67+), which was in strong correlation with the expression of activation markers. Finally, the level of T cell anergy, as assessed by the proliferative responses to CD3 stimulation and to a panel of microbial Ags, proved to be comparable in HIV-1 and HIV-2 patients with a similar degree of CD4 depletion despite large differences in viral load. Our data are consistent with a direct causal relationship between immune activation and CD4 cell depletion in HIV disease and an only indirect relation of these parameters to the virus replication rate. Invoking the concept of proximal immune activation and virus transmission, which links efficient transmission of virus to local cell activation and proliferation in response to Ags and inflammation, we propose an integrative interpretation of the data and suggest that strongly elevated immune activation induces CD4 cell depletion and not vice versa, with potential implications for the choice of treatment strategies.

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Low Plasma Human Immunodeficiency Virus Type 2 Viral Load Is Independent of Proviral Load: Low Virus Production In Vivo

Cited by 128 publications

References 34 publications

Rate of Increase in Circulating IL-7 and Loss of IL-7Rα Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes

Rate of Increase in Circulating IL-7 and Loss of IL-7Rα Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes

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

CD4 T Cell Depletion Is Linked Directly to Immune Activation in the Pathogenesis of HIV-1 and HIV-2 but Only Indirectly to the Viral Load

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