title: HIV-1 gp120 protein downregulates Nef induced IL-6 release in immature dentritic cells through interplay of DC-SIGN.
abstract: HIV-1 replication is a tightly controlled mechanism which demands the interplay of host as well as viral factors. Both gp120 (envelope glycoprotein) and Nef (regulatory protein) have been correlated with the development of AIDS disease in independent studies. In this context, the ability of HIV-1 to utilize immature dentritic cells for transfer of virus is pivotal for early pathogenesis. The presence of C-type lectins on dendritic cells (DCs) like DC-SIGN, are crucial in inducing antiviral immunity to HIV-1. Both gp120 and Nef induce the release of cytokines leading to multiple effects of viral pathogenesis. Our study elucidated for the first time the cross-talk of the signaling mechanism of these two viral proteins in immature monocyte derived dentritic cells (immDCs). Further, gp120 was found to downregulate the IL-6 release by Nef, depending on the interaction with DC-SIGN. A cascade of signaling followed thereafter, including the activation of SOCS-3, to mediate the diminishing effect of gp120. Our results also revealed that the anti-apoptotic signals emanated from Nef was put to halt by gp120 through inhibition of Nef induced STAT3. Thus our results implicate that the signaling generated by gp120 and Nef, undergoes a switch-over mechanism that significantly contributes to the pathogenesis of HIV-1 and widens our view towards the approach on battling the viral infection.
authors.affiliation: Division of Virology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Roni
authors.initials: R
authors.lastname: Sarkar
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Sekhar
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D017209:Apoptosis; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D015536:Down-Regulation; D015870:Gene Expression; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D034622:RNA Interference; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D015850:Interleukin-6; D037181:Lectins, C-Type; D016328:NF-kappa B; D019908:Proto-Oncogene Proteins c-raf; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C106644:SOCS3 protein, human
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