Early events in retrovirus XMRV infection of the wild-derived mouse Mus pahari

Toshie Sakuma, Jason M. Tonne, Karen A. Squillace, Seiga Ohmine, Tayaramma Thatava, Kah-Whye Peng, Michael A Barry, Yasuhiro H Ikeda

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

A novel gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), has been identified in patients with prostate cancer and in patients with chronic fatigue syndromes. Standard Mus musculus laboratory mice lack a functional XPR1 receptor for XMRV and are therefore not a suitable model for the virus. In contrast, Gairdner's shrew-mice (Mus pahari) do express functional XPR1. To determine whether Mus pahari could serve as a model for XMRV, primary Mus pahari fibroblasts and mice were infected with cell-free XMRV. Infection of cells in vitro resulted in XMRV Gag expression and the production of XMRV virions. After intraperitoneal injection of XMRV into Mus pahari mice, XMRV proviral DNA could be detected in spleen, blood, and brain. Intravenous administration of a green fluorescent protein (GFP) vector pseudotyped with XMRV produced GFP+ CD4+ T cells and CD19+ B cells. Mice mounted adaptive immune responses against XMRV, as evidenced by the production of neutralizing and Env- and Gag-specific antibodies. Prominent G-to-A hypermutations were also found in viral genomes isolated from the spleen, suggesting intracellular restriction of XMRV infection by APOBEC3 in vivo. These data demonstrate infection of Mus pahari by XMRV, potential cell tropism of the virus, and immunological and intracellular restriction of virus infection in vivo. These data support the use of Mus pahari as a model for XMRV pathogenesis and as a platform for vaccine and drug development against this potential human pathogen.

Original languageEnglish (US)
Pages (from-to)1205-1213
Number of pages9
JournalJournal of Virology
Volume85
Issue number3
DOIs
StatePublished - Feb 2011

Fingerprint

Xenotropic murine leukemia virus-related virus
Retroviridae
Gammaretrovirus
Mus
Virus Diseases
viruses
mice
infection
Green Fluorescent Proteins
green fluorescent protein
Spleen
spleen
Shrews
Viruses
Chronic Fatigue Syndrome
Tropism
Viral Genome

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Sakuma, T., Tonne, J. M., Squillace, K. A., Ohmine, S., Thatava, T., Peng, K-W., ... Ikeda, Y. H. (2011). Early events in retrovirus XMRV infection of the wild-derived mouse Mus pahari. Journal of Virology, 85(3), 1205-1213. https://doi.org/10.1128/JVI.00886-10

Early events in retrovirus XMRV infection of the wild-derived mouse Mus pahari. / Sakuma, Toshie; Tonne, Jason M.; Squillace, Karen A.; Ohmine, Seiga; Thatava, Tayaramma; Peng, Kah-Whye; Barry, Michael A; Ikeda, Yasuhiro H.

In: Journal of Virology, Vol. 85, No. 3, 02.2011, p. 1205-1213.

Research output: Contribution to journalArticle

Sakuma, T, Tonne, JM, Squillace, KA, Ohmine, S, Thatava, T, Peng, K-W, Barry, MA & Ikeda, YH 2011, 'Early events in retrovirus XMRV infection of the wild-derived mouse Mus pahari', Journal of Virology, vol. 85, no. 3, pp. 1205-1213. https://doi.org/10.1128/JVI.00886-10
Sakuma, Toshie ; Tonne, Jason M. ; Squillace, Karen A. ; Ohmine, Seiga ; Thatava, Tayaramma ; Peng, Kah-Whye ; Barry, Michael A ; Ikeda, Yasuhiro H. / Early events in retrovirus XMRV infection of the wild-derived mouse Mus pahari. In: Journal of Virology. 2011 ; Vol. 85, No. 3. pp. 1205-1213.
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