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CD24 and Fc fusion protein protects SIVmac239-infected Chinese rhesus macaque against progression to AIDS

Authors :
Martin Devenport
Yang Liu
Ming-Xu Zhang
Pan Zheng
Wei Pang
Xiao-Liang Zhang
Jian-Ping Ma
Xiao-Dong Lian
Lin-Tao Zhang
Yong-Tang Zheng
Mei Ye
Liguo Zhang
Mingyue Liu
Ren-Rong Tian
Peng Zhang
Hong-Yi Zheng
Gao-Hong Zhang
Source :
Antiviral research. 157
Publication Year :
2018

Abstract

Chronic immune activation and systemic inflammation are underlying causes of acquired immunodeficiency syndrome (AIDS). Products of virus replication and microbial translocation, co-infection or opportunistic pathogens, and danger-associated molecular patterns have been reported to contribute to chronic immune activation and inflammation in human immunodeficiency virus type-1/simian immunodeficiency virus (HIV-1/SIV) infection or other disease. To develop new strategies and therapies for HIV-1/AIDS, we tested if the CD24 and Fc fusion protein (CD24Fc), which interacts with danger-associated molecular patterns and sialic acid binding Ig-like lectin to attenuate inflammation, can protect Chinese rhesus macaques (ChRMs) with SIV infection. We found that CD24Fc treatment decreased weight loss, wasting syndrome, intractable diarrhea, and AIDS morbidity and mortality, while it was well tolerated by SIV-infected animals. Corresponding to the elimination of intractable diarrhea, CD24Fc significantly reduced the expression of IL-6 and indoleamine 2, 3-dioxygenase-1 in peripheral blood mononuclear cell and inflammation in the ileum, colon and rectum based on the reduction of inflammatory cells, pathological scores and expression of inflammatory cytokines. Furthermore, although CD24Fc did not restore CD4+ T cell number or significantly change T cell subsets or CD4+ T cell activation, it maintained low levels of plasma soluble CD14, CD8+ T cell activation, viral load and proviral load in the peripheral blood mononuclear cells and marrow. These results suggested that CD24Fc confers protection to SIV-infected ChRMs against progression to AIDS. It was also implied that CD24Fc may be a potential therapeutic approach for the control of HIV-1/AIDS.

Details

ISSN :
18729096
Volume :
157
Database :
OpenAIRE
Journal :
Antiviral research
Accession number :
edsair.doi.dedup.....cb25ff23236bbc978c68b1f9f2b710db