(P5) The inhibitory effect of HIV-1 specific CD8+ T cells on the establishment and maintenance of HIV-1 latent reservoir

Författare/Medförfattare

Xi Chen[1,2]*Ujjwal Neogi[2]*Kai Deng[1]

Affiliates

Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.[1] Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.[2]

Abstract

Combination antiretroviral therapy (cART) halts HIV-1 replication but fails to eliminate the virus because of the presence of a stable latent viral reservoir. Interruption of cART leads to a rapid rebound of viremia. Therefore life-long treatment is required. Efforts to purge the latent reservoir have focused on taking full advantage of the immune system, such as HIV-1 specific CD8+ T cells and antibody-mediated killing by NK cells or macrophages. However, the susceptibility of latently infected cells to viral-specific CD8+ T cells in different stages of infection is not fully assessed. Here by using a patient-derived primary cell model of HIV-1 latency, we show that latent infection can be hardly established in CD4+ T cells if functional HIV-1-specific CD8+ T cells were presented shortly after infection. And if the latent infection is already established, viral-specific CD8+ T cells still can efficiently kill latently infected CD4+ T cells, even in the absence of latency-reversing agents. Our data strongly demonstrates the importance of boosting effective CD8+ T cell responses, either in acute infection to prevent the formation of a latent reservoir, or during chronic infection to clear latently infected cells.