IL-7 up-regulates HIV-1 replication in naturally infected peripheral blood mononuclear cells.
We have investigated the effect of exogenous IL-7 on replication of HIV-1 in PBMCs isolated from asymptomatic, chronically infected donors. We show that IL-7 induced virus replication and increased proviral DNA levels in CD8- PBMC cultures. IL-7 also increased the levels of doubly spliced HIV-1 tat RNA in these cultures. In comparison, IL-2 induced lower levels of virus production than IL-7, but had a more pronounced effect on cell proliferation. The IL-7-mediated increase in virus replication was not inhibited by neutralizing mAbs to IL-1 beta, IL-2, IL-6, or TNF-alpha, and was only partially dependent on ligation of the T cell accessory molecule CD28. CD8+ cells inhibited the increase in viral replication following IL-7 stimulation, but did not prevent virus replication following ligation of CD3 in the presence of IL-7. The data shows that IL-7 regulates HIV-1 replication in naturally infected PBMCs.
Smithgall
M D
MD
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
Wong
J G
JG
Critchett
K E
KE
Haffar
O K
OK
D000998:Antiviral Agents / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors; D015756:Genes, tat / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015851:Interleukin-7 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D000998:Antiviral Agents; D018106:CD28 Antigens; D016207:Cytokines; D015851:Interleukin-7; D012333:RNA, Messenger