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PMID: 20211031 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

High systemic levels of interleukin-10, interleukin-22 and C-reactive protein in Indian patients are associated with low in vitro replication of HIV-1 subtype C viruses.

Retrovirology ·Vol. 7 ·2010-03-09 ·Pages 15

Arias JF, Nishihara R, Bala M, Ikuta K

Abstract

HIV-1 subtype C (HIV-1C) accounts for almost 50% of all HIV-1 infections worldwide and predominates in countries with the highest case-loads globally. Functional studies suggest that HIV-1C is unique in its biological properties, and there are contradicting reports about its replicative characteristics. The present study was conducted to evaluate whether the host cytokine environment modulates the in vitro replication capacity of HIV-1C viruses. A small subset of HIV-1C isolates showing efficient replication in peripheral blood mononuclear cells (PBMC) is described, and the association of in vitro replication capacity with disease progression markers and the host cytokine response was evaluated. Viruses were isolated from patient samples, and the corresponding in vitro growth kinetics were determined by monitoring for p24 production. Genotype, phenotype and co-receptor usage were determined for all isolates, while clinical category, CD4 cell counts and viral loads were recorded for all patients. Plasmatic concentrations of cytokines and, acute-phase response, and microbial translocation markers were determined; and the effect of cytokine treatment on in vitro replication rates was also measured. We identified a small number of viral isolates showing high in vitro replication capacity in healthy-donor PBMC. HIV-1C usage of CXCR4 co-receptor was rare; therefore, it did not account for the differences in replication potential observed. There was also no correlation between the in vitro replication capacity of HIV-1C isolates and patients' disease status. Efficient virus growth was significantly associated with low interleukin-10 (IL-10), interleukin-22 (IL-22), and C-reactive protein (CRP) levels in plasma (p < .0001). In vitro, pretreatment of virus cultures with IL-10 and CRP resulted in a significant reduction of virus production, whereas IL-22, which lacks action on immune cells appears to mediate its anti-HIV effect through interaction with both IL-10 and CRP, and its own protective effect on mucosal membranes. These results indicate that high systemic levels of IL-10, CRP and IL-22 in HIV-1C-infected Indian patients are associated with low viral replication in vitro, and that the former two have direct inhibitory effects whereas the latter acts through downstream mechanisms that remain uncertain.

MeSH Terms
Adolescent Adult C-Reactive Protein/analysis CD4 Lymphocyte Count Cells, Cultured Child Female Genotype HIV Infections/immunology,virology HIV-1/classification,genetics,isolation & purification,physiology Humans India Interleukin-10/blood Interleukins/blood Leukocytes, Mononuclear/immunology,virology Male Middle Aged Receptors, HIV/analysis Viral Load Virus Replication Young Adult
Chemicals
IL10 protein, human Interleukins Receptors, HIV Interleukin-10 C-Reactive Protein interleukin-22
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Arias Juan F
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Nishihara Reiko
Bala Manju
Ikuta Kazuyoshi
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Article Info
Journal
Retrovirology
Abbr.
Retrovirology
ISSN
1742-4690
Published
2010-03-09
Epub
2010-00-09
Pages
15
Language
English
Region
England
NLM ID
101216893
PMCID
PMC2841095
Subset
IM
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