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This Article Free via Open Access: OA OA Free Full Text Full Text (PDF) OA All Versions of this Article: vir.0.010603-0v1 90/6/1461    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Gill, M. B. Articles by Stevenson, P. G. PubMed PubMed Citation Articles by Gill, M. B. Articles by Stevenson, P. G. Agricola Articles by Gill, M. B. Articles by Stevenson, P. G.

Murid herpesvirus-4 lacking thymidine kinase reveals route-dependent requirements for host colonization

Christopher M. Smith

Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK

Correspondence
Philip G. Stevenson
pgs27{at}cam.ac.uk

Gammaherpesviruses infect at least 90 % of the world's population. Infection control is difficult, in part because some fundamental features of host colonization remain unknown, for example whether normal latency establishment requires viral lytic functions. Since human gammaherpesviruses have narrow species tropisms, answering such questions requires animal models. Murid herpesvirus-4 (MuHV-4) provides one of the most tractable. MuHV-4 genomes delivered to the lung or peritoneum persist without lytic replication. However, they fail to disseminate systemically, suggesting that the outcome is inoculation route-dependent. After upper respiratory tract inoculation, MuHV-4 infects mice without involving the lungs or peritoneum. We examined whether host entry by this less invasive route requires the viral thymidine kinase (TK), a gene classically essential for lytic replication in terminally differentiated cells. MuHV-4 TK knockouts delivered to the lung or peritoneum were attenuated but still reached lymphoid tissue. In contrast, TK knockouts delivered to the upper respiratory tract largely failed to establish a detectable infection. Therefore TK, and by implication lytic replication, is required for MuHV-4 to establish a significant infection by a non-invasive route.

Present address: CSL Limited, Melbourne, Australia.

This article has been cited by other articles:

				P. G. Stevenson, J. P. Simas, and S. Efstathiou Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4 J. Gen. Virol., October 1, 2009; 90(10): 2317 - 2330. [Abstract] [Full Text] [PDF]