Large isoform of mammalian relative of dnaJ is a major determinant of human susceptibility to HIV-1 infection

Yu Ping Chiang, Wang Huei Sheng, Pei Lan Shao, Ya Hui Chi, Yi Ming Arthur Chen, Szu Wei Huang, Hsiu Ming Shih, Luan Yin Chang, Chun Yi Lu, Shan Chwen Chang, Chien Ching Hung, Li Min Huang

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4 Citations (Scopus)

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 ofMRJ-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.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalEBioMedicine
Volume1
Issue number2-3
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Keywords

  • Human immunodeficiency virus type 1 (HIV-1)
  • Macrophages
  • Mammalian relative of dnaj (MRJ)
  • Susceptibility to infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Chiang, Y. P., Sheng, W. H., Shao, P. L., Chi, Y. H., Arthur Chen, Y. M., Huang, S. W., Shih, H. M., Chang, L. Y., Lu, C. Y., Chang, S. C., Hung, C. C., & Huang, L. M. (2014). Large isoform of mammalian relative of dnaJ is a major determinant of human susceptibility to HIV-1 infection. EBioMedicine, 1(2-3), 126-132. https://doi.org/10.1016/j.ebiom.2014.10.002