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Journal of Virology, February 2004, p. 1730-1738, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1730-1738.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Low Doses of Hepadnavirus Induce Infection of the Lymphatic System That Does Not Engage the Liver

Tomasz I. Michalak,1,2* Patricia M. Mulrooney,1 and Carla S. Coffin1

Molecular Virology and Hepatology Research, Division of Basic Medical Sciences,1 Division of Pathology, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada2

Received 5 August 2003/ Accepted 27 October 2003

Woodchuck hepatitis virus (WHV), which is closely related to human hepatitis B virus and is considered to be principally hepatotropic, invades the host's lymphatic system and persists in lymphoid cells independently of whether the infection is symptomatic and serologically evident or concealed. In this study, we show, with the woodchuck model of hepatitis B, that hepadnavirus can establish an infection that engages the lymphatic system, but not the liver, and persists in the absence of virus serological markers, including antiviral antibodies. This primary occult infection is caused by wild-type virus invading the host at a quantity usually not greater than 103 virions. It is characterized by trace virus replication progressing in lymphatic organs and peripheral lymphoid cells that, with time, may also spread to the liver. The infection is transmissible to virus-naive hosts as an asymptomatic, indefinitely long, occult carriage of small amounts of biologically competent virus. In contrast to residual silent WHV persistence, which normally endures after the resolution of viral hepatitis and involves the liver, primary occult infection restricted to the lymphatic system does not protect against reinfection with a large, liver-pathogenic WHV dose; however, the occult infection is associated with a swift recovery from hepatitis caused by the superinfection. Our study documents that the lymphatic system is the primary target of WHV infection when small quantities of virions invade a susceptible host.

* Corresponding author. Mailing address: Molecular Virology and Hepatology Research, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6. Phone: (709) 777-7301. Fax: (709) 777-8279. E-mail: timich{at}mun.ca.

Journal of Virology, February 2004, p. 1730-1738, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1730-1738.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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