Dependence of CD8+ T-cell-mediated suppression of HIV type 1 on viral phenotypes and mediation of phenotype-dependent suppression by viral envelope gene and not by beta-chemokines.
CD8+ T-cell-mediated HIV-1 suppressive activity has been shown against a number of strains of HIV-1 and HIV-2. In this study using a semiquantitative assay, we showed that CD8+ T cells from seropositive subjects and herpes virus saimiri transformed CD8+ T-cell clones from HIV-1-infected subjects exhibited 5 to 100-fold higher suppressive activity against slow replicating nonsyncytia-inducing strains (Slow/NSI) as compared to fast replicating syncytia-inducing strains (Fast/SI) of HIV-1. Such differential suppressive activity was not due to beta-chemokines as evidenced by the lack of blocking activity of antibodies to RANTES, MIP-1beta, and MIP-1alpha on the antiviral activities of CD8+ T cells. Moreover, there was no correlation between the level of CD8+ T-cell suppression and the level of these beta-chemokines in culture supernatant. Results from the CD8+ T-cell-mediated suppressive activity against two molecular cloned virus ME1 (Slow/NSI), ME46 (Fast/SI), and their interstrain recombinants indicate that the envelope gene carries a major genetic determinant responsible for this phenotypic-dependent differential suppressive activity.
Chen
Y
Y
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.
Dampf
D
D
Chen
M
M
Kulka
K
K
Volsky
D J
DJ
Saha
K
K
Gupta
P
P
D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D019742:Chemokines, CC / Q000378:metabolism*; D015331:Cohort Studies; D003602:Cytotoxicity, Immunologic; D015726:Giant Cells / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D019742:Chemokines, CC; D014759:Viral Envelope Proteins