Restriction of HIV replication in infected T cells and monocytes by interferon-alpha.
Human recombinant interferon-alpha (IFN alpha) restricted viral replication in human immunodeficiency virus- (HIV) infected T cells and monocytes. With T cells, reverse transcriptase (RT) activity in culture fluids was reduced threefold from that of control infected cells by IFN treatment, but HIV p24 antigen levels were unchanged. In contrast, levels of p24 antigen and RT activity in lysates of IFN-treated infected cells were threefold greater than those of controls. These differences suggest that the mechanism for IFN-induced antiviral effects in HIV-infected T cells resides in the terminal events (assembly and release) of the virus replication cycle. Monocytes treated with IFN at the time of virus challenge showed no p24 antigen or RT activity, no HIV-specific mRNA, and no proviral DNA in cells for up to 3 weeks after infection. IFN treatment of chronically infected monocytes also decreased virus replication, as assessed by p24 antigen, mRNA and RT detection assays. However, levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency.
Gendelman
H E
HE
Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD 20852.
Baca
L
L
Turpin
J A
JA
Kalter
D C
DC
Hansen
B D
BD
Orenstein
J M
JM
Friedman
R M
RM
Meltzer
M S
MS
D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D015683:Gene Products, gag / Q000276:immunology; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D015488:HIV Antigens / Q000032:analysis; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology*; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology*; D014758:Viral Core Proteins / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D007370:Interferon Type I; D012367:RNA, Viral; D011994:Recombinant Proteins; D014758:Viral Core Proteins