Epigenetic silencing of CD4 expression in nonpathogenic SIV infection in African green monkeys

摘要: African green monkeys (AGMs) are natural hosts of SIV that postthymically downregulate CD4 to maintain a large population CD4-CD8aa+ virus-resistant cells with Th functionality, which can result in AGMs becoming apparently cured SIVagm infection. To understand the mechanisms this process, we performed genome-wide transcriptional analysis on T induced vitro from and closely related patas expression rhesus macaques. In downregulated CD4, pathway revealed an atypical regulation DNA methylation machinery, was reversible when pharmacologically targeted 5-aza-2 deoxycytidine. This signature driven largely by dioxygenase TET3, became loss expression. CpG motifs within AGM promoter region methylated during downregulation were stably imprinted sorted directly ex vivo. These results suggest use epigenetic durably silence gene. Manipulation these could provide avenues for modulating HIV-1 entry receptor become progressively infected SIV, lead novel therapeutic interventions aimed reduce HIV viremia