Noninfectious papilloma virus-like particles inhibit HIV-1 replication: implications for immune control of HIV-1 infection by IL-27.
Human papilloma virus (HPV)-like particles (VLPs) have been used as a vaccine to prevent HPV infection. Recent studies demonstrate that VLPs bind to dendritic cells and induce the expression of antiviral cytokines such as interferon-alpha (IFN-alpha), interleukin-10 (IL-10) and IFN-gamma. In the present study, we evaluated the effect of VLPs on HIV-1 replication in peripheral blood mononuclear cells (PBMCs), CD4+ T cells, and macrophages. Here, we show that VLPs suppress the replication of both X4 and R5 HIV-1 without affecting the expression of CD4, CXCR4, and CCR5. Soluble factor(s) released by PBMCs and macrophages on VLPs treatment inhibited HIV-1 replication. To determine the inhibitory factors, DNA microarray analysis was performed using VLP-treated PBMCs and macrophages. VLPs induced the genes associated with IFN induction, immune responses, and antiviral responses, among with the recently described cytokine IL-27. Subsequently, IL-27 was found to be a potent inhibitor of HIV-1 replication in PBMCs, CD4+ T cells, and macrophages. Taken together, our studies identify a novel role of IL-27 in restricting HIV-1 replication and suggest that further examination of the inhibitory property of IL-27 may pave the way for a novel therapy for HIV-1 infection.
Fakruddin
J Mohamad
JM
Laboratory of Human Retrovirology, Clinical Services Program (CSP), Science Applications International Corporation (SAIC)-Frederick, National Cancer Institute (NCI), MD, USA.
Lempicki
Richard A
RA
Gorelick
Robert J
RJ
Yang
Jun
J
Adelsberger
Joseph W
JW
Garcia-Pineres
Alfonso J
AJ
Pinto
Ligia A
LA
Lane
H Clifford
HC
Imamichi
Tomozumi
T
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D003429:Cross Reactions; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015728:Receptors, HIV / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014771:Virion / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects
D007378:Interleukins; C464565:MYDGF protein, human; D015728:Receptors, HIV