Influence of prothymosin-alpha on HIV-1 target cells.
The important role of CD8(+) T cells in controlling HIV-1 infection through the innate as well as the adaptive immune system is well established. In addition to the major histocompatibility complex (MHC)-dependent cytotoxic activity of CD8(+) T cells, they produce soluble factors that suppress HIV-1 replication in an MHC-independent manner. Several of those factors have been identified, including beta-chemokines, Rantes, MIP-1alpha, MIP-1beta, and MDC. We previously identified that prothymosin alpha (ProTalpha) in the conditioned medium of HVS transformed CD8(+) T cells was a potent inhibitor of HIV-1 replication following proviral integration. In this report we further characterize the anti-HIV-1 activity of ProTalpha by demonstrating its target-cell specificity, distinction from additional inhibitors of HIV-1 transcription in CD8(+) T cell supernatants, as well as the differential regulation of host cell antiviral genes that could impact HIV-1 replication. These genes include a number of transcription factors as well IFN-alpha-inducible genes including PKR, IRF1, and Rantes, in the absence of induction of IFN-alpha. These data suggest that the anti-HIV-1 activity of ProTalpha is mediated through the modulation of a number of genes that have been reported to suppress HIV-1 replication including the dysregulation of transcription factors and the induction of PKR and Rantes mRNA.
Mosoian
Arevik
A
Division of Infectious Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Teixeira
Avelino
A
Burns
Colin S
CS
Khitrov
Gregory
G
Zhang
Weijia
W
Gusella
Luca
L
Klotman
Paul
P
Klotman
Mary
M
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D008285:Major Histocompatibility Complex; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
D011498:Protein Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; C040782:prothymosin alpha; D013947:Thymosin