HIV-1 integration is inhibited by stimulation of the VPAC2 neuroendocrine receptor.
Successful HIV-1 infection requires a number of specific stages leading to integration of the provirus. We previously suggested that members of the VPAC neuroendocrine receptor family may play a role in HIV-1 infection. We now show that stimulation of the VPAC2 receptor with specific agonists provides strong resistance to HIV-1 infection. Daily stimulation of VPAC2, but not VPAC1 or PAC1, resulted in up to 90% inhibition of X4 or R5 productive infections in either cell lines or PBMCs. VPAC2 agonist stimulation had no effect on cell surface co-receptors, the rate of apoptotic cells, or HIV-1 entry or reverse transcription of viral RNA. However, we provide evidence that VPAC2-specific agonists inhibit HIV-1 infection through an inhibitory effect on the ability of the HIV-1 cDNA to integrate into the host DNA. These data reveal that VPAC2 agonists are appropriate candidates for further study as possible treatments aimed at the amelioration of HIV/AIDS.
Bokaei
Payman Baradar
PB
The Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5G 2M1.
Ma
Xue-Zhong
XZ
Sakac
Darinka
D
Branch
Donald R
DR
D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D017930:Genes, Reporter; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000821:virology; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000819:agonists; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000819:agonists*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000819:agonists; D048348:Reverse Transcription; D016662:Virus Integration / Q000502:physiology*; D053586:Virus Internalization
D016655:HIV Core Protein p24; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I