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

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.sup.+] T cells and macrophages, were present throughout the BLT mouse brain. HIV DNA, HIV RNA, and/or [p24.sup.+] cells were observed in the brains of HIV-infected animals, regardless of the HIV isolate used. HIV infection resulted in decreased numbers of [CD4.sup.+] T cells, increased numbers of [CD8.sup.+] T cells, and a decreased [CD4.sup.+]/[CD8.sup.+]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.sup.+] T cell depletion and a reduced [CD4.sup.+]/[CD8.sup.+] 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.
Introduction The advent and widespread use of effective antiretroviral therapy (ART) to treat HIV infection has dramatically curtailed the severity of the neurocognitive impairment previously observed in HIV-infected patients (1). [...]