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Volume 5, Issue 6(Suppl) J Infect Dis Ther, an open access journal
ISSN: 2332-0877 Euro Infectious Diseases 2017
September 07-09, 2017
September 07-09, 2017 | Paris, France
Infectious Diseases
6th Euro-Global Conference on
The anti-HIV candidate abx464 dampens intestinal inflammation by triggering il22 production in activated
Macrophages
Jamal Tazi
University of Montpellier , France
The progression of human immunodeficiency virus (HIV) is associated with mucosal damage in the gastrointestinal (GI) tract.
This damage enables bacterial translocation from the gut and leads to subsequent inflammation. Dextran sulphate sodium
(DSS-treatment) is an established animal model for experimental colitis that was recently shown to recapitulate the link between
GI-tract damage and pathogenic features of SIV infection. The current study tested the protective properties of ABX464, a first-in-
class anti-HIV drug candidate that has demonstrated anti-viral activity in HIV treatment of naïve patients. ABX464 also induced a
long-lasting control of the viral load in HIV infected humanized mice after treatment arrest. ABX464 treatment strongly attenuated
DSS-induced colitis in mice and produced a long-term protection against prolonged DSS-exposure after drug cessation. Consistently,
ABX464 reduced the colonic production of the inflammatory cytokines IL-6 and TNF as well as that of the chemoattractant MCP-
1. However, RNA profiling analysis revealed the capacity of ABX464 to induce the expression of IL-22, a cytokine involved in colitis
tissue repair both in DSS-treated mice. A comprehensive analysis of the gene expression profiles by RNAseq demonstrated that the
expression of IL22 was preferentially induced by ABX464 in mouse bone marrow derived macrophages only upon stimulation with
LPS. Importantly, anti-IL22 antibodies abrogated the protective effect of ABX464 on colitis in DSS-treated mice. Because reduced
IL-22 production in the gut mucosa is an established factor of HIV and DSS-induced immunopathogenesis, our data suggest that the
anti-inflammatory properties of ABX464 warrant exploration in both HIV and inflammatory ulcerative colitis (UC) disease. In the
DSS induced colitis model, ABX464 protects mice from inflammatory response by prevention of weight loss and colon size, reduced
macrophage recruitment into the intestine, decreased levels of pro-inflammatory cytokines and long-lasting effect (like in the HIV
humanized mouse model)
Biography
Jamal Tazi is Professor of Functional Genomics at the University of Montpellier and Deputy Director of the Health Centre Biology "Rabelais" responsible for
education and training. For 20 years, he led the team "messenger RNA metabolism in metazoans" within the Institute for Molecular Genetics in Montpellier (IGMM)
where he made important contributions to understand the fundamental mechanisms of the expression of our genes and editing of their products. These discoveries
are used today in the medical field through the development of a new therapy based on the use of small molecules to fight against viral infections. To ensure
the transition between basic and applied research, and also to support these innovative projects to clinical stage, Hel founded in 2008 the company Splicos and
established its partnership with public institutions as a cooperative laboratory where, he became the Scientific Director
Jamal Tazi, J Infect Dis Ther 2017, 5:6(Suppl)
DOI: 10.4172/2332-0877-C1-032