The latest study from the Jill Roberts Institute, "The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation," was published on September 6 in Nature. To read more, click here.     Dr. Gregory Sonnenberg wins inaugural award from the Society for Mucosal Immunology. To read more, click here.  The Kenneth Rainin Foundation awarded Dr. Iliyan Iliev and colleagues from Mount Sinai a $250,000 Synergy Award to examine the composition of the fungal community in babies born to mothers with inflammatory bowel disease. To read more, click here. Dr. Randy Longman received the Irma T. Hirschl Career Scientist Award and the New York Crohn’s Foundation Award.    

The Jill Roberts Institute for Research in Inflammatory Bowel Disease

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Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction.

TitleProthymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction.
Publication TypeJournal Article
Year of Publication2010
AuthorsMosoian, A, Teixeira, A, Burns, CS, Sander, LE, G Gusella, L, He, C, J Blander, M, Klotman, P, Klotman, ME
JournalProc Natl Acad Sci U S A
Volume107
Issue22
Pagination10178-83
Date Published2010 Jun 01
ISSN1091-6490
KeywordsAdaptor Proteins, Vesicular Transport, Amino Acid Sequence, Animals, Anti-HIV Agents, CD8-Positive T-Lymphocytes, HIV-1, Humans, Immunity, Innate, In Vitro Techniques, Interferon Type I, Ligands, Macrophages, Mice, Mice, Knockout, Molecular Sequence Data, Myeloid Differentiation Factor 88, Protein Precursors, Recombinant Proteins, RNA, Messenger, Sequence Homology, Amino Acid, Thymosin, Toll-Like Receptor 4, Tumor Necrosis Factor-alpha, Virus Replication
Abstract

Induction of type I interferons (IFN) is a central feature of innate immune responses to microbial pathogens and is mediated via Toll-like receptor (TLR)-dependent and -independent pathways. Prothymosin-alpha (ProTalpha), a small acidic protein produced and released by CD8(+) T cells, inhibits HIV-1, although the mechanism for its antiviral activity was not known. We demonstrate that exogenous ProTalpha acts as a ligand for TLR4 and stimulates type I IFN production to potently suppress HIV-1 after entry into cells. These activities are induced by native and recombinant ProTalpha, retained by an acidic peptide derived from ProTalpha, and lost in the absence of TLR4. Furthermore, we demonstrate that ProTalpha accounts for some of the soluble postintegration HIV-1 inhibitory activity long ascribed to CD8(+) cells. Thus, a protein produced by CD8(+) T cells of the adaptive immune system can exert potent viral suppressive activity through an innate immune response. Understanding the mechanism of IFN induction by ProTalpha may provide therapeutic leads for IFN-sensitive viruses.

DOI10.1073/pnas.0914870107
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID20479248
PubMed Central IDPMC2890444
Grant ListR21 AI076092 / AI / NIAID NIH HHS / United States
AI76092-01A1 / AI / NIAID NIH HHS / United States