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IP-10 Promotes Latent HIV Infection in Resting Memory CD4(+) T Cells via LIMK-Cofilin Pathway

A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4(+) T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have inve...

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Detalles Bibliográficos
Autores principales: Wang, Zhuo, Yin, Xiaowan, Ma, Meichen, Ge, Hongchi, Lang, Bin, Sun, Hong, He, Sijia, Fu, Yajing, Sun, Yu, Yu, Xiaowen, Zhang, Zining, Cui, Hualu, Han, Xiaoxu, Xu, Junjie, Ding, Haibo, Chu, Zhenxing, Shang, Hong, Wu, Yuntao, Jiang, Yongjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383741/
https://www.ncbi.nlm.nih.gov/pubmed/34447368
http://dx.doi.org/10.3389/fimmu.2021.656663
Descripción
Sumario:A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4(+) T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have investigated the role of IP-10 in the establishment of HIV reservoirs in CD4(+) T cells, and found that in HIV-infected individuals, plasma IP-10 was elevated, and positively correlated with HIV viral load and viral reservoir size. In addition, we found that binding of IP-10 to CXCR3 enhanced HIV latent infection of resting CD4(+) T cells in vitro. Mechanistically, IP-10 stimulation promoted cofilin activity and actin dynamics, facilitating HIV entry and DNA integration. Moreover, treatment of resting CD4(+) T cells with a LIM kinase inhibitor R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. These results suggest that IP-10 is a critical factor involved in HIV latent infection, and that therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.