title: Large Isoform of Mammalian Relative of DnaJ is a Major Determinant of Human Susceptibility to HIV-1 Infection.
abstract: Individual differences in susceptibility to human immunodeficiency virus type 1 (HIV-1) infection have been of interest for decades. We aimed to determine the contribution of large isoform of Mammalian DnaJ (MRJ-L), a HIV-1 Vpr-interacting cellular protein, to this natural variation. Expression of MRJ-L in monocyte-derived macrophages was significantly higher in HIV-infected individuals (n = 31) than their uninfected counterparts (n = 27) (p = 0.009). Fifty male homosexual subjects (20 of them are HIV-1 positive) were further recruited to examine the association between MRJ-L levels and occurrence of HIV infection. Bayesian multiple logistic regression revealed that playing a receptive role and increased levels of MRJ-L in macrophages were two risk factors for HIV-1 infection. A 1% rise in MRJ-L expression was associated with a 1.13 fold (95% CrI 1.06-1.29) increase in odds of contracting HIV-1 infection. Ex vivo experiments revealed that MRJ-L facilitated Vpr-dependent nuclear localization of virus. Infection of macrophage-tropic strain is a critical step in HIV-1 transmission. MRJ-L is a critical factor in this process; hence, subjects with higher macrophage MRJ-L levels are more vulnerable to HIV-1 infection.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Chiang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Wang-Huei
authors.initials: WH
authors.lastname: Sheng
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: Shao
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 350, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chi
authors.affiliation: Center for Infectious Diseases and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Ming Arthur
authors.initials: YM
authors.lastname: Chen
authors.affiliation: Center for Infectious Diseases and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Szu-Wei
authors.initials: SW
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hsiu-Ming
authors.initials: HM
authors.lastname: Shih
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Luan-Yin
authors.initials: LY
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Chien-Ching
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
keywords: Human immunodeficiency virus type 1 (HIV-1); Macrophages; Mammalian relative of DnaJ (MRJ); Susceptibility to infection