Journal
EBIOMEDICINE
Volume 1, Issue 2-3, Pages 126-132Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2014.10.002
Keywords
Human immunodeficiency virus type 1 (HIV-1); Macrophages; Mammalian relative of DnaJ (MRJ); Susceptibility to infection
Funding
- National Health Research Institutes, Taiwan [NHRI-EX100-10053SI]
- National Taiwan University Hospital [97-A109]
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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 ofmacrophage-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. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license
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