期刊
JOURNAL OF VIROLOGY
卷 82, 期 1, 页码 471-486出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00939-07
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资金
- NATIONAL CANCER INSTITUTE [R01CA058093] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK045909] Funding Source: NIH RePORTER
- Biotechnology and Biological Sciences Research Council [BB/E005896/1] Funding Source: Medline
- Medical Research Council [G0200585] Funding Source: Medline
- NCI NIH HHS [R01 CA058093, R01CA58093] Funding Source: Medline
- NIDDK NIH HHS [R01DK45909, R01 DK045909] Funding Source: Medline
- BBSRC [BB/E005896/1] Funding Source: UKRI
- MRC [G0200585] Funding Source: UKRI
Understanding why human immunodeficiency virus (HIV) preferentially infects some CD4(+) CD45RO(+) memory T cells has implications for antiviral immunity and pathogenesis. We report that differential expression of a novel secreted factor, ps20, previously implicated in tissue remodeling, may underlie why some CD4 T cells are preferentially targeted. We show that (i) there is a significant positive correlation between endogenous ps20 mRNA in diverse CD4 T-cell populations and in vitro infection, (ii) a ps20(+) permissive cell can be made less permissive by antibody blockade- or small-interference RNA-mediated knockdown of endogenous ps20, and (iii) conversely, a ps20(low) cell can be more permissive by adding ps20 exogenously or engineering stable ps20 expression by retroviral transduction. ps20 expression is normally detectable in CD4 T cells after in vitro activation and interleukin-2 expansion, and such oligocional populations comprise ps20(positive) and ps20(low/negative) isogenic clones at an early differentiation stage (CD45RO(+)/CD25(+)/CD28(+)/CD57(-)). This pattern is altered in chronic HIV infection, where ex vivo CD4+ CD45RO+ T cells express elevated ps20. ps20 promoted HIV entry via fusion and augmented CD54 integrin expression; both of these effects were reversed by anti-ps20 antibody. We therefore propose ps20 to be a novel signature of HIV-permissive CD4 T cells that promotes infection in an autocrine and paracrine manner and that HIV has coopted a fundamental role of ps20 in promoting cell adhesion for its benefit. Disrupting the ps20 pathway may therefore provide a novel anti-HIV strategy.
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