We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)–associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

Chronic hepatitis B virus (HBV) infection can result in severe liver disease with eventual progression to cirrhosis and hepatocellular carcinoma. 1 Roughly 5% of the world' s population (over 350 million persons) are chronically infected with HBV. 2 Although interferon alfa remains the only licensed drug for the treatment of chronic HBV infection, the overall response rate to this immunotherapy is less than 40%. 3 Therefore, other effective antiviral therapies for patients with HBV infection are needed.Lamivudine [(-)2Ј-deoxy-3Ј-thiacytidine, 3TC] is a member of a class of antiviral nucleoside analogs that inhibit hepadnavirus replication specifically by terminating viral DNA synthesis. 4 Lamivudine is currently being evaluated in Phase III clinical trials for the treatment of both patients chronically infected with HBV and patients with HBV reinfection of an allograft after orthotopic liver transplantation.In Phase II trials, 5-7 lamivudine treatment was shown to rapidly reduce serum HBV DNA to levels below the detection limit of standard commercial assays, and to be well tolerated with no major toxicities. However, as with other antivirals, 7-11 resistance to lamivudine therapy can emerge in some patients. Recent investigations have reported the development of lamivudine-resistant HBV in six orthotopic liver transplantation patients on therapy. [12][13][14] In each patient, sequence analysis of serum HBV DNA revealed the presence of specific mutations in the tyrosine, methionine, aspartate, aspartate (YMDD) amino acid motif of the viral polymerase. This YMDD motif is a conserved domain of all reverse transcriptases (RT) and is required for polymerization activity. However, various other amino acid changes in the polymerase were also described in these reports.To determine the significance of various mutations in the development of lamivudine-resistant HBV, a more comprehensive study was undertaken. In this study, DNA sequences were determined from HBV isolates from 20 patients experiencing breakthrough HBV reactivation while on lamivudine therapy. From this larger series of 20 clinical HBV isolates, the database of lamivudine-resistant HBV sequences was expanded to confirm viral DNA mutations associated with lamivudine resistance in vivo. To explore the biological significance of the key observed mutations, putative resis-