Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5

Clerici, Mario; Buttò, Stefano; Lukwiya, Matthew; Saresella, Marina; Declich, Silvia; Trabattoni, Daria; Pastori, Claudia; Piconi, Stefania; Fracasso, Claudio; Fabiani, Massimo; Ferrante, Pasquale; Rizzardini, Giuliano; Lopalco, Lucia

doi:10.1097/00002030-200009290-00003

Cited by 116 publications

(100 citation statements)

References 32 publications

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“…1). In accordance with other studies of individuals living in rural Africa (4,8,19), basal immune activation levels were high and were significantly increased by HIV-2 infection. In the selected patients, as well as in the rest of the HIV-2 cohort, immune activation levels for both CD4 and CD8 lymphocytes were correlated with the viral load in Ps and showed a significant difference between NPs and Ps ( Fig.…”

Section: Resultssupporting

confidence: 92%

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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Section: Resultssupporting

confidence: 92%

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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“…Third, immune activation (largely measured as increased expression of CD38 þ and HLA-DR þ on T-cells) has also been shown to be inversely correlated with IL-7Ra expression on CD4 T-cells in HIV-infected patients, 45,46 and immune activation has a negative impact on CD4 T-cell recovery. [47][48][49] Although we did not compare the immune activation levels in the UARTO and Caucasian patients, numerous studies have described a higher degree of immune activation both in HIVuninfected [50][51][52][53][54] and HIV-infected African patients [53][54][55][56] as compared with patients from high-income countries owing to differences in the environment 52 and prevalence of other co-infections. 51 The combined effects of poorer CD4 T-cell gain owing to increased T-cell activation and a reduced expression of IL-7Ra on T-cells may potentially negate any beneficial effects of increased IL-7 availability.…”

Section: Discussionmentioning

confidence: 95%

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

et al. 2011

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We previously found an association between faster CD4 þ T-cell recovery in HIV-infected patients receiving combination antiretroviral therapy (cART) and interleukin-7 receptor-a (IL-7Ra) haplotype-2 in a predominantly Caucasian cohort. This study aims to determine whether this association was also significant in Africans. Patients were recruited from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort (n ¼ 352). We used survival analysis and linear mixed modelling (LMM) to determine factors associated with CD4 T-cell recovery. Eight IL-7Ra single-nucleotide polymorphisms (SNPs) were genotyped in both Africans and Caucasians (n ¼ 57). Soluble (s)IL-7Ra levels were measured by ELISA. In UARTO, IL-7Ra haplotype-2 was associated with slower CD4 T-cell recovery following cART by using survival analysis (P ¼ 0.020) and no association was found with LMM (P ¼ 0.958). The tagging-SNP for IL-7Ra haplotype-2 (rs6897932) was associated with decreased sIL-7Ra (Po0.001). The haplotypes for the IL-7Ra were significantly different in Africans and Caucasians. Using IL-7Ra genotypes we found slower CD4 T-cell recovery in UARTO patients was still associated with rs6897932 (P ¼ 0.009) and rs3194051 was associated with faster CD4 T-cell recovery (P ¼ 0.006). Unlike Caucasians, we did not demonstrate a significant association between IL-7Ra haplotype 2 and faster CD4 T-cell recovery in Africans. The IL-7Ra SNPs associated with CD4 T-cell recovery following cART differ in African and Caucasian cohorts.

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“…This high viral load seen in our population may be due to the constant immune activation that is driven environmentally. [10] Increased HIV replication in activated CD4…”

Section: It Is Reported That the Mean Cd4mentioning

confidence: 99%

“…[10][11] In this context, it was found that the AUC for the viral loads were low when compared to CD4 + T cells indicating lower accuracy of viral load levels in classifying different CDC categories.…”

Section: It Is Reported That the Mean Cd4mentioning

confidence: 99%

Evidence for lower CD4<sup><b>+</sup></b> T cell and higher viral load in asymptomatic HIV-1 infected individuals of India: Implications for therapy initiation

Kannangai¹,

Kandathil²,

Ebenezer³

et al. 2008

Indian J Med Microbiol

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Purpose: We have earlier documented that the south Indian population had lower CD4 counts. The aim of this study was to investigate a previous suggestion on a new CD4 + T cell cut off and association with HIV-1 RNA levels for decision on anti retroviral therapy in India (south). Methods: We evaluated a new methodology i.e., artus real-time PCR and CD4 + T cell count by Guava EasyCD4™ system. From 146 HIV infected individuals seen at a tertiary care centre, blood was collected for CD4+ T cell and HIV-1 RNA estimation. Results: The receiver operating characteristic curve cut off value for the CD4 counts to distinguish between CDC clinical categories A and B was 243 cells/μL, and to distinguish B and C was 153 cells/μL. The RNA level that differentiated CDC A and B was 327473 RNA copies/mL, while for CDC B and C was 688543 copies/mL. There was a signiÞ cant negative correlation (r = -0.55, P < 0.01) between the RNA estimated and CD4+ T cell counts in HIV infected individuals. Conclusions: A majority with CD4 counts of 201-350 cells/μL in our population had higher viral load than the treatment threshold suggested by the International AIDS society and the above two methodologies are useful in monitoring HIV infections.

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Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5

Cited by 116 publications

References 32 publications

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

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

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

Evidence for lower CD4<sup><b>+</sup></b> T cell and higher viral load in asymptomatic HIV-1 infected individuals of India: Implications for therapy initiation

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