Increased in vitro replication of CC chemokine receptor 5-restricted human immunodeficiency virus type 1 primary isolates in Th2 lymphocytes may correlate with AIDS progression.
It has been found that infection of target cells with the CC chemokine receptor 5-restricted (R5) human immunodeficiency virus type 1 (HIV-1) isolate requires the presence of CD4 and CCR5 molecules on the surface of target cells. We observed that R5 HIV-1 primary isolates from long term survivors replicate less efficiently than the same variants from AIDS progressors in Th1 and Th2 lymphocytes. Real-time quantitative polymerase chain reaction (RQ-PCR) of reverse transcribed messenger RNA, revealed approximately 2 times higher level of CCR5 transcript in Th1 than Th2 cells. Nevertheless we found that R5 HIV-1 primary isolates from long-term survivors and AIDS progressors replicated more efficiently in Th2 than Th1 lymphocytes. These findings correlated with lower-level biosynthesis of regulated upon activation, normal T-cell expressed and secreted (RANTES), and macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha, MIP-1beta), in Th2 than Th1 lymphocytes. Our data indicates that Th0/Th2 cell orientation in HIV-infected individuals and a higher replication of R5 HIV-1 primary isolates in AIDS progressors than long term-survivors can be associated with progression to AIDS.
Ofori
Harold
H
University of Medical Sciences, Department of Biochemistry and Molecular Biology, 60-781 Poznań, Poland.
Jagodziński
Paweł P
PP
D000328:Adult; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D018946:Chemokine CCL5; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000401:mortality*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D019713:Receptors, CCR5 / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D012720:Severity of Illness Index; D016019:Survival Analysis; D018418:Th2 Cells / Q000378:metabolism / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
D015415:Biomarkers; D018946:Chemokine CCL5; D019713:Receptors, CCR5