Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells | Zendy

Hann Low | Zendy; Nigora Mukhamedova | Zendy; Huanhuan Cui | Zendy; Brian P. McSharry | Zendy; Selmir Avdic | Zendy; Anh Hoang | Zendy; Michael Ditiatkovski | Zendy; Yingying Liu | Zendy; Ying Fu | Zendy; Peter J. Meikle | Zendy; Martin Blomberg | Zendy; Konstantinos A. Polyzos | Zendy; William E. Miller | Zendy; Piotr Religa | Zendy; Michael Bukrinsky | Zendy; Cecilia SöderbergNauclér | Zendy; Barry Slobedman | Zendy; Dmitri Sviridov | Zendy

Open Access

Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells

Author(s) -

Hann Low,

Nigora Mukhamedova,

Huanhuan Cui,

Brian P. McSharry,

Selmir Avdic,

Anh Hoang,

Michael Ditiatkovski,

Yingying Liu,

Ying Fu,

Peter J. Meikle,

Martin Blomberg,

Konstantinos A. Polyzos,

William E. Miller,

Piotr Religa,

Michael Bukrinsky,

Cecilia SöderbergNauclér,

Barry Slobedman,

Dmitri Sviridov

Publication year - 2016

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2016.05.070

Subject(s) - lipid raft , microbiology and biotechnology , abca1 , cholesterol , efflux , lipid metabolism , cdc42 , biology , human cytomegalovirus , lipidome , reverse cholesterol transport , chemistry , lipoprotein , actin , biochemistry , virus , signal transduction , immunology , gene , transporter

Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, HCMV infection increased the efflux of cellular cholesterol, despite reducing the abundance of ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association of actin with lipid rafts, and leading to a dramatic change in the abundance and/or structure of lipid rafts. These changes displaced ABCA1 from the cell surface but created new binding sites for apolipoprotein A-I, resulting in enhanced cholesterol efflux. The changes also reduced the inflammatory response in macrophages. HCMV infection modified the host lipidome profile and expression of several genes and microRNAs involved in cholesterol metabolism. In mice, murine CMV infection elevated plasma triglycerides but did not affect the level and functionality of high-density lipoprotein. Thus, HCMV, through its protein US28, reorganizes lipid rafts and disturbs cell cholesterol metabolism.

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