期刊
VIRUS RESEARCH
卷 240, 期 -, 页码 166-174出版社
ELSEVIER
DOI: 10.1016/j.virusres.2017.08.009
关键词
Hepatitis B virus; HBx protein; Exosome; Hepatic stellate cells; Liver disease; Neutral sphingomyelinase2
类别
资金
- Department of Science and Technology, Govt. of India [SB/FTS/LS-181/2012]
- Council of Scientific and Industrial Research, Govt. of India [27(0277)/12/EMR-II]
- Department of Science and Technology, Government of India [SR/S2/JCB-80/2012]
The cellular secretory vesicles known as 'exosomes' have emerged as key player in intercellular transport and communication between different eukaryotic in order to maintain body homeostasis. Many pathogenic viruses utilize exosome pathway to efficiently transfer bioactive components from infected cells to na ve cells. Here, we show that HBx can tweak the exosome biogenesis machinery both by enhancing neutral sphingomyelinase2 activity as well as by interacting with exosomal biomarkers such as neutral sphingomyelinase2, CD9 and CD81. The nano particle tracking analysis revealed enhanced secretion of exosomes by the HBx-expressing cells while confocal studies confirmed the co-localization of HBx with CD9 and CD63. Importantly, we observed the encapsulation of HBx mRNA and protein in these exosomes besides some other qualitative changes. The exosomal cargo secreted by HBx-expressing cells had a profound effect on the recipient hepatic cells including creation of a milieu conducive for cellular-transformation. Thus, the present study unfolds a novel role of HBx in intercellular communication by facilitating horizontal transfer of viral gene products and other host factors via exosomes in order to support viral spread and pathogenesis.
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