BST2/tetherin enhances entry of human cytomegalovirus

Kasinath Viswanathan, M. Shane Smith, Daniel Malouli, Mandana Mansouri, Jay Nelson, Klaus Frueh

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.

Original languageEnglish (US)
Article numbere1002332
JournalPLoS Pathogens
Volume7
Issue number11
DOIs
StatePublished - Nov 2011

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Cytomegalovirus
Virion
Cell Membrane
Ebolavirus
Human Herpesvirus 8
Viral Genes
Cytomegalovirus Infections
Viral Proteins
Interferons
Small Interfering RNA
Antiviral Agents
HIV-1
Monocytes
Proteins
Fibroblasts
Viruses
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

BST2/tetherin enhances entry of human cytomegalovirus. / Viswanathan, Kasinath; Smith, M. Shane; Malouli, Daniel; Mansouri, Mandana; Nelson, Jay; Frueh, Klaus.

In: PLoS Pathogens, Vol. 7, No. 11, e1002332, 11.2011.

Research output: Contribution to journalArticle

Viswanathan, K, Smith, MS, Malouli, D, Mansouri, M, Nelson, J & Frueh, K 2011, 'BST2/tetherin enhances entry of human cytomegalovirus', PLoS Pathogens, vol. 7, no. 11, e1002332. https://doi.org/10.1371/journal.ppat.1002332
Viswanathan, Kasinath ; Smith, M. Shane ; Malouli, Daniel ; Mansouri, Mandana ; Nelson, Jay ; Frueh, Klaus. / BST2/tetherin enhances entry of human cytomegalovirus. In: PLoS Pathogens. 2011 ; Vol. 7, No. 11.
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