Grape seed extract proanthocyanidins downregulate HIV-1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells.
Flavonoids and related polyphenols, in addition to their cardioprotective, anti-tumor, anti-inflammatory, anti-carcinogenic and anti-allergic activities, also possess promising anti-HIV effects. Recent studies documented that the beta-chemokine receptors, CCR2b, CCR3 and CCR5, and the alpha-chemokine receptors, CXCR1, CXCR2 and CXCR4 serve as entry coreceptors for HIV-1. Although flavonoids and polyphenolic compounds elicit anti-HIV effects such as inhibition of HIV-1 expression and virus replication, the molecular mechanisms underlying these effects remain to be clearly elucidated. We hypothesize that flavonoids exert their anti-HIV effects, possibly by interfering at the HIV co-receptor level. We investigated the effect of flavonoid constituents of a proprietary grape seed extract (GSE) on the expression of HIV-1 coentry receptors by immunocompetent mononuclear leukocytes. Our results showed that GSE significantly downregulated the expression of the HIV-1 entry co-receptors, CCR2b, CCR3 and CCR5 in normal PBMC in a dose dependent manner. Further, GSE treated cultures showed significantly lower number of CCR3 positive cells as quantitated by flow cytometry analysis which supports RT-PCR gene expression data. Investigations of the mechanisms underlying the anti-HIV-1 effects of grape seed extracts may help to identify promising natural products useful in the prevention and/or amelioration of HIV-1 infection.
Nair
Madhavan P
MP
Departments of Medicine and Microbiology, Kaleida Health System, Buffalo General Hospital, Buffalo, NY, USA. mnair@acsu.buffalo.edu
Kandaswami
Chithan
C
Mahajan
Supriya
S
Nair
Harikrishna N
HN
Chawda
Ram
R
Shanahan
Thomas
T
Schwartz
Stanley A
SA
D000872:Anthocyanins / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000187:drug effects / Q000235:genetics; D019707:Receptors, Chemokine / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012639:Seeds / Q000737:chemistry; D027843:Vitis / Q000737:chemistry*
D000872:Anthocyanins; D000975:Antioxidants; C515334:CCR2 protein, human; C515350:CCR3 protein, human; D010936:Plant Extracts; D044945:Proanthocyanidins; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C013221:proanthocyanidin