期刊
MOLECULAR IMMUNOLOGY
卷 148, 期 -, 页码 68-80出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2022.04.018
关键词
HIV-1; Macrophages; Inflammasome; Viral Infection; Immune Evasion
资金
- Sa?o Paulo Research Foundation, Brazil (FAPESP) [2011/12199-0, 2015/04342-9, 2018/15066-0]
- Sao Paulo Research Foundation, Brazil (FAPESP) [2011/12199-0, 2015/04342-9, 2018/15066-0]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES) [2011/12199-0]
- [001]
The successful establishment of HIV-1 infection is related to the blocking or inactivation of inflammasomes. This study found that resting HIV-1-infected macrophages release pro-inflammatory cytokines and show increased CXCL10 expression. The HIV-1 proteins Gag and Vpr interact with host proteins, preventing the activation of inflammasomes and effective immune responses.
The successful establishment of HIV-1 infection is related to inflammasome blocking or inactivation, which can result in the viral evasion of the immune responses and formation of reservoirs in several tissues. In this sense, we aimed to evaluate the viral and cellular mechanisms activated during HIV-1 infection in human primary macrophages that allow an effective viral replication in these cells. We found that resting HIV-1-infected macrophages, but not those activated in classical or alternative patterns, released IL-1 beta and other pro-inflammatory cytokines, and showed increased CXCL10 expression, without changes in the NLRP3, AIM2 or RIG-I inflammasome pathways. Also, similar levels of Casp-1, phosphorylated NF-kappa B (p65) and NLRP3 proteins were found in uninfected and HIV-1-infected macrophages. Likewise, no alterations were detected in ASC specks released in the culture supernatant after HIV-1 infection, suggesting that macrophages remain viable after infection. Using in silico prediction studies, we found that the HIV-1 proteins Gag and Vpr interact with several host proteins. Comparable levels of trans-LTB4 were found in the supernatants of uninfected and HIV-1-infected macrophages, whereas ROS production was impaired in infected cells, which was not reversed after the PMA stimulus. Immunofluorescence analysis showed structural alterations in the mitochondrial architecture and an increase of BIM in the cytoplasm of infected cells. Our data suggest that HIV-1 proteins Gag and Vpr, through interacting with cellular proteins in the early steps of infection, preclude the inflammasome activation and the development of effective immune responses, thus allowing the establishment of the infection.
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