Transcriptome analysis of CD4^(+)T cells from HIV-infected individuals receiving ART with LLV revealed novel transcription factors regulating HIV-1 promoter activity  

作　　者：Jingliang Chen Yaozu He Huolin Zhong Fengyu Hu Yonghong Li Yeyang Zhang Xia Zhang Weiyin Lin Quanmin Li Feilong Xu Shaozhen Chen Hui Zhang Weiping Cai Linghua Li 

机构地区：[1]Guangzhou Eighth People's Hospital,Guangzhou Medical University,Guangzhou,510060,China [2]Institute of Human Virology,Key Laboratory of Tropical Disease Control of Ministry Education,Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China [3]Guangzhou Laboratory,Bio-Island,Guangzhou,510320,China

出　　处：《Virologica Sinica》2023年第3期398-408,共11页中国病毒学（英文版）

基　　金：the Ethics Committee of Guangzhou Eighth People's Hospital(202033166),and all participants provided written informed consent.

摘　　要：Some HIV-infected individuals receiving ART develop low-level viremia(LLV),with a plasma viral load of 50-1000 copies/mL.Persistent low-level viremia is associated with subsequent virologic failure.The peripheral blood CD4^(+)T cell pool is a source of LLV.However,the intrinsic characteristics of CD4^(+)T cells in LLV which may contribute to low-level viremia are largely unknown.We analyzed the transcriptome profiling of peripheral blood CD4^(+)T cells from healthy controls(HC)and HIV-infected patients receiving ART with either virologic sup-pression(VS)or LLV.To identify pathways potentially responding to increasing viral loads from HC to VS and to LLV,KEGG pathways of differentially expressed genes(DEGs)were acquired by comparing VS with HC(VS-HC group)and LLV with VS(LLV-VS group),and overlapped pathways were analyzed.Characterization of DEGs in key overlapping pathways showed that CD4^(+)T cells in LLV expressed higher levels of Th1 signature transcription factors(TBX21),toll-like receptors(TLR-4,-6,-7 and-8),anti-HIV entry chemokines(CCL3 and CCL4),and anti-IL-1βfactors(ILRN and IL1R2)compared to VS.Our results also indicated activation of the NF-κB and TNF signaling pathways that could promote HIV-1 transcription.Finally,we evaluated the effects of 4 and 17 tran-scription factors that were upregulated in the VS-HC and LLV-VS groups,respectively,on HIV-1 promoter activity.Functional studies revealed that CXXC5 significantly increased,while SOX5 markedly suppressed HIV-1 tran-scription.In summary,we found that CD4^(+)T cells in LLV displayed a distinct mRNA profiling compared to that in VS,which promoted HIV-1 replication and r+eactivation of viral latency and may eventually contribute to virologic failure in patients with persistent LLV.CXXC5 and SOX5 may serve as targets for the development of latency-reversing agents.

关 键 词：HIV-1 Low-level viremia(LLV) TRANSCRIPTOME HIV-1 promoter CXXC5 SOX5 

分 类 号：R512.91[医药卫生—内科学]