TY - JOUR
T1 - Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection
AU - Shan, Liang
AU - Deng, Kai
AU - Gao, Hongbo
AU - Xing, Sifei
AU - Capoferri, Adam A.
AU - Durand, Christine M.
AU - Rabi, S. Alireza
AU - Laird, Gregory M.
AU - Kim, Michelle
AU - Hosmane, Nina N.
AU - Yang, Hung Chih
AU - Zhang, Hao
AU - Margolick, Joseph B.
AU - Li, Linghua
AU - Cai, Weiping
AU - Ke, Ruian
AU - Flavell, Richard A.
AU - Siliciano, Janet D.
AU - Siliciano, Robert F.
N1 - Funding Information:
We thank all study participants for making this research possible. R.F.S. was supported by the NIH Martin Delaney I4C (UM1 AI126603), Beat-HIV ( UM1 AI126620 ), and DARE ( UM1 AI12661 ). Collaboratories by the Johns Hopkins Center for AIDS Research ( P30AI094189 ), by NIH grant 43222, and by the Howard Hughes Medical Institute and the Bill and Melinda Gates Foundation ( OPP1115715 ). L.S. is supported by NIH 1K99AI125065-01 and Mathilde Krim Fellowship, amfAR . K.D. is supported by National Natural Science Foundation of China ( 81672024 ), by Guangdong Innovative and Entrepreneurial Research Team Program ( 2016ZT06S638 ), and by Joint-Innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou ( 201508020256 ).
Publisher Copyright:
© 2017
PY - 2017/10/17
Y1 - 2017/10/17
N2 - The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4+ T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4+ T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4+ T cells. Establishment of latent HIV-1 infection in CD4+ T could be inhibited by viral-specific CD8+ T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. The latent reservoir for HIV is a barrier to cure, but it is unclear why HIV establishes latency given its ability to evade immune responses through evolution. Shan et al. show that latency is an unfortunate consequence of infection of CD4+ T cells within a narrow time window after activation.
AB - The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4+ T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4+ T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4+ T cells. Establishment of latent HIV-1 infection in CD4+ T could be inhibited by viral-specific CD8+ T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines. The latent reservoir for HIV is a barrier to cure, but it is unclear why HIV establishes latency given its ability to evade immune responses through evolution. Shan et al. show that latency is an unfortunate consequence of infection of CD4+ T cells within a narrow time window after activation.
UR - http://www.scopus.com/inward/record.url?scp=85032811754&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2017.09.014
DO - 10.1016/j.immuni.2017.09.014
M3 - Article
C2 - 29045905
AN - SCOPUS:85032811754
SN - 1074-7613
VL - 47
SP - 766-775.e3
JO - Immunity
JF - Immunity
IS - 4
ER -