Format

Send to

Choose Destination
J Clin Invest. 2018 Jul 2;128(7):2862-2876. doi: 10.1172/JCI98968. Epub 2018 Jun 4.

T cells establish and maintain CNS viral infection in HIV-infected humanized mice.

Author information

1
Division of Infectious Diseases, Center for AIDS Research (CFAR), University of North Carolina at Chapel Hill (UNC-CH), School of Medicine, Chapel Hill, North Carolina, USA.
2
Department of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
3
Department of Nutrition, UNC-CH, Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.

Abstract

The human brain is an important site of HIV replication and persistence during antiretroviral therapy (ART). Direct evaluation of HIV infection in the brains of otherwise healthy individuals is not feasible; therefore, we performed a large-scale study of bone marrow/liver/thymus (BLT) humanized mice as an in vivo model to study HIV infection in the brain. Human immune cells, including CD4+ T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or p24+ cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of CD4+ T cells, increased numbers of CD8+ T cells, and a decreased CD4+/CD8+ T cell ratio in the brain. Using humanized T cell-only mice (ToM), we demonstrated that T cells establish and maintain HIV infection of the brain in the complete absence of human myeloid cells. HIV infection of ToM resulted in CD4+ T cell depletion and a reduced CD4+/CD8+ T cell ratio. ART significantly reduced HIV levels in the BLT mouse brain, and the immune cell populations present were indistinguishable from those of uninfected controls, which demonstrated the effectiveness of ART in controlling HIV replication in the CNS and returning cellular homeostasis to a pre-HIV state.

KEYWORDS:

AIDS/HIV; Infectious disease; Macrophages; T cells

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center