title: Heroin use is associated with lower levels of restriction factors and type I interferon expression and facilitates HIV-1 replication.
abstract: Heroin use is associated with increased incidence of infectious diseases such as HIV-1 infection, as a result of immunosuppression to a certain extent. Host restriction factors are recently identified cellular proteins with potent antiviral activities. Whether heroin use impacts on the in vivo expression of restriction factors that result in facilitating HIV-1 replication is poorly understood. Here we recruited 432 intravenous drug users (IDUs) and 164 non-IDUs at high-risk behaviors. Based on serological tests, significantly higher prevalence of HIV-1 infection was observed among IDUs compared with non-IDUs. We included those IDUs and non-IDUs without HIV-1 infection, and found IDUs had significantly lower levels of TRIM5α, TRIM22, APOBEC3G, and IFN-α, -β expression than did non-IDUs. We also directly examined plasma viral load in HIV-1 mono-infected IDUs and non-IDUs and found HIV-1 mono-infected IDUs had significantly higher plasma viral load than did non-IDUs. Moreover, intrinsically positive correlation between type I interferon and TRIM5α or TRIM22 was observed, however, which was dysregulated following heroin use. Collectively, heroin use benefits HIV-1 replication that may be partly due to suppression of host restriction factors and type I interferon expression.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Jia-Wu
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Feng-Liang
authors.initials: FL
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Clinical Laboratory, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.
authors.forename: De-Yao
authors.initials: DY
authors.lastname: Deng
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China. Electronic address: zhengyt@mail.kiz.ac.cn.
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D000071480:APOBEC-3G Deaminase / Q000097:blood; D000328:Adult; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000254:growth & development*; D003932:Heroin / Q000494:pharmacology*; D006556:Heroin Dependence / Q000503:physiopathology; D006801:Humans; D007165:Immunosuppression Therapy; D016898:Interferon-alpha / Q000097:blood*; D016899:Interferon-beta / Q000097:blood*; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000097:blood; D012097:Repressor Proteins / Q000097:blood; D000070584:Tripartite Motif Proteins / Q000097:blood; D044767:Ubiquitin-Protein Ligases; D019562:Viral Load / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D016898:Interferon-alpha; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D000070584:Tripartite Motif Proteins; D003932:Heroin; D016899:Interferon-beta; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human
keywords: APOBEC3G; Heroin use; TRIM22; TRIM5α; Type I interferon