Increased level of IL-32 during human immunodeficiency virus infection suppresses HIV replication.
Interleukin-32 was recently identified as a pro-inflammatory cytokine produced by T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes. IL-32 is induced by IFN-gamma in a time-dependent manner suggesting a role for IL-32 in innate and adaptive immune responses. In this study we present evidence that Human immunodeficiency virus promotes interleukin-32 production at both mRNA and protein levels. Our results showed that there is a 74% increase in the serum levels of IL-32 among HIV patients as compared to healthy individuals. There was a three-fold increase in the promoter activity of the IL-32 in the present infections HIV clone. This increase in IL-32 promoter activity was substantiated by increased IL-32 mRNA and protein levels. We have also demonstrated that IL-32 suppresses HIV replication. Our results show that HIV LTR activity was increased by more than six-folds when endogenous IL-32 was knocked down by IL-32-specific siRNA whereas it decreased by one-fold when IL-32 was over expressed in the cells. Similarly a more than two-fold increase and a 50% decrease in HIV p24 values were noted when IL-32 was knocked down and when IL-32 was over expressed in the cells, respectively. Our present work shows that raised IL-32 levels in HIV infection may in turn hamper HIV replication; one of the protective mechanisms of nature.
Rasool
Sahibzada T
ST
Medical Virology Laboratory, The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, Hubei, PR China.
Tang
Heng
H
Wu
Jianmei
J
Li
Wei
W
Mukhtar
Muhammad Mahmood
MM
Zhang
Jingwen
J
Mu
Yongxin
Y
Xing
Huang Xioa
HX
Wu
Jianguo
J
Zhu
Ying
Y
D002460:Cell Line; D003001:Cloning, Molecular; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006678:HIV / Q000502:physiology*; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000276:immunology*; D016325:HIV Long Terminal Repeat / Q000235:genetics / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014779:Virus Replication / Q000276:immunology*
D016655:HIV Core Protein p24; C496971:IL32 protein, human; D007378:Interleukins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins