HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA

• 成果类型: Article
• 署名作者: Capoferri, Adam A.; Wiegand, Ann; Hong, Feiyu; Jacobs, Jana L.; Spindler, Jonathan; Musick, Andrew; Bale, Michael J.; Shao, Wei; Sobolewski, Michele D.; Cillo, Anthony R.; Luke, Brian T.; Fennessey, Christine M.; Gorelick, Robert J.; Hoh, Rebecca; Halvas, Elias K.; Deeks, Steven G.; Coffin, John M.; Mellors, John W.; Kearney, Mary F.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Georgetown University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; Cornell University; Weill Cornell Medicine; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Frederick National Laboratory for Cancer Research; University of California System; University of California San Francisco; Tufts University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12559
• DOI: 10.1073/pnas.2405210121
• 发表日期: 2024-09-03
• 关键词: cd4(+) t-cells; proviruses produce; intact hiv-1; dna; individuals; progression; activation; reservoir; virus

摘要

In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non- controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV- 1 unspliced and quantitative single- cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34- fold fewer infected cells per million PBMC. These results reveal that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. will help to refine strategies toward achieving HIV remission without ART.