Raehtz Kevin D, Pandrea Ivona, Apetrei Cristian
Department of Pathology, School of Medicine.
Department of Infectious Diseases and Microbiology, Graduate School of Public Health.
Curr Opin HIV AIDS. 2025 Mar 1;20(2):124-132. doi: 10.1097/COH.0000000000000911. Epub 2025 Jan 8.
Typically, both HIV-infected humans and simian immunodeficiency virus (SIV)-infected Asian nonhuman primates (NHPs) eventually progress to AIDS, while African NHPs that are natural hosts of SIV do not, in spite of life-long, high levels of viral replication. Lack of disease progression in African NHPs is not due to some adaptation by the virus, but rather to host adaptations to the virus. Central to these adaptations is maintenance of the gut integrity during acute viral replication and inflammation, which allows natural hosts to avoid the chronic inflammation characteristic to pathogenic HIV/SIV infection.
It has been recently shown that natural hosts of SIVs, such as the African green monkey (AGM), avoid damage to the mucosal epithelium through wound healing mechanisms, possibly with the contribution of a unique anti-inflammatory microbiome. Furthermore, these mechanisms are independent of viral replication, and CD4 + T-cell activation or depletion.
Future SIV research on natural hosts should focus on further elucidating the anti-inflammatory state of their gut, and the role of microbiome/dysbiosis in the pathogenesis of SIV infection, with the goal of development new regiments or treatments to reduce or even halt the vicious cycle of gut damage and inflammation triggered by pathogenic HIV/SIV infection.
通常,感染人类免疫缺陷病毒(HIV)的人和感染猿猴免疫缺陷病毒(SIV)的亚洲非人灵长类动物(NHP)最终都会发展为艾滋病,而作为SIV天然宿主的非洲NHP尽管终生存在高水平的病毒复制,但却不会发展为艾滋病。非洲NHP不发生疾病进展并非由于病毒的某些适应性变化,而是宿主对病毒的适应性变化。这些适应性变化的核心是在急性病毒复制和炎症期间维持肠道完整性,这使得天然宿主能够避免致病性HIV/SIV感染所特有的慢性炎症。
最近的研究表明,SIV的天然宿主,如非洲绿猴(AGM),通过伤口愈合机制避免对黏膜上皮造成损伤,这可能得益于独特的抗炎微生物群的作用。此外,这些机制独立于病毒复制、CD4 + T细胞激活或耗竭。
未来关于SIV天然宿主的研究应集中于进一步阐明其肠道的抗炎状态,以及微生物群/生态失调在SIV感染发病机制中的作用,目标是开发新的方案或治疗方法,以减少甚至阻止致病性HIV/SIV感染引发的肠道损伤和炎症的恶性循环。