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  • The distribution of MRJ L levels

    2018-10-25

    The distribution of MRJ-L levels seemed to be bimodal in uninfected general population (Figs. 1c and 2). This observation implicated that the expression levels of MRJ-L in macrophages may be regulated by genetic or epigenetic processes, which require future investigation. Furthermore, in vitro infection of HIV-1 for 8days did not affect MRJ-L level in primary macrophages (Fig. 1d). This evidence strongly suggests that MRJ-L levels should be independent of HIV-1 infection. MSM, especially those who practice RUAI, are known to be at particularly high risk for HIV-1 infection (Silan et al., 2013). Our results show that high levels of MRJ-L in macrophages (41.5 fold) are as strong a risk factor as anal intercourse (43.9 fold) for HIV-1 acquisition. MRJ has two isoforms, a large form (MRJ-L or DnaJB6) and a small form (MRJ-S) (Hanai and Mashima, 2003). The two variants are likely products of alternatively spliced mRNAs. The large form, MRJ-L, is 326 amino rac protein long and possesses a nuclear localization signal, while the small MRJ-S lacks the carboxyl-terminal 95 amino acids of MRJ-L but contains an additional of 10 amino acids (KEQLLRLDNK). Despite the differences at the carboxyl terminus, both isoforms share similar structures with a conserved J domain (70 amino acids) and a glycine/phenylalanine domain (Liberek et al., 1991). MRJ-S mainly localizes to the cytoplasm while MRJ-L distributes both to the cytosol and the nucleus (Cheetham et al., 1992). It has been suggested that the conserved DNAJ domain was responsible for HSP40\'s ability to inhibit HIV-1 production (Urano et al., 2013). Our results show that a significant correlation is found between levels of macrophage MRJ-L expression and levels of HIV-1 infection among high-risk subjects. Therefore, natural variation in MRJ-L levels in macrophages and unprotected sex behavior may be the major determinants of susceptibility to HIV-1 infection.
    Author Contributions
    Declaration of Interests
    Role of the Funding Source This project was funded by the National Health Research Institutes, Taiwan (NHRI-EX100-10053SI) and supported by an A1 project grant (97-A109 Establishment of Molecular Virology Lab) from the National Taiwan University Hospital. The funding sources had no involvement in the design, collection, analysis, interpretation, writing, or decision to submit the article.
    Acknowledgments
    Introduction Although measles is now a vaccine-preventable disease, it remains one of the leading causes of death in children, especially in resource-poor regions of the world (Moss and Griffin, 2006; Nandy et al., 2006; Wolfson et al., 2009). Therefore, it is very important to control the measles in order to improve child health worldwide. Measles is a highly contagious respiratory viral disease characterized by the appearance of fever and a rash that can be very serious. Although improvements have been made to the control of measles worldwide by the WHO, large-scale outbreaks have recently been observed, particularly in developing countries including those of Southeast Asia (Simons et al., 2012; Perry et al., 2014). The measles virus (MV) is a single-stranded, negative-sense RNA virus, belonging to the genus Morbillivirus, family Paramyxoviridae. It consists of 15,894 nucleotides (nt) encoding six structural proteins. Although MV is thought to be serologically monotypic, high genetic variability in the N and H genes has been known. In particular, the 450 nt C-terminus of the N gene is the target area for MV genotyping recommended by the WHO (Expanded Programme on Immunization (EPI), 1998; Anon., 2005, 2006, 2012). Sniadack et al. reported on large-scale measles epidemics in Vietnam during 2008–2010 (Sniadack et al., 2011). However, detailed molecular-based epidemiologic studies on MV circulating in Vietnam have not yet appeared. Genetic information of the viruses has been used in molecular epidemiologic studies to identify the transmission pathways and the route of infection. Therefore, genetic surveillance of the MV has provided a means to measure the success of the measles control program (Liffick et al., 2001).