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

Division of Virology

¹ E-mail: pgs27{at}cam.ac.uk

Gamma-herpesviruses 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 gamma-herpesviruses 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 asked here 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.

Received 28 January 2009; accepted 27 February 2009.

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]