A NEW HEPADNAVIRUS ENDEMIC IN ARCTIC GROUND-SQUIRRELS IN ALASKA

We present evidence for a novel member of the hepadnavirus family that is endemic in wild arctic ground squirrels (Spermophylus parryi kenni cotti) in Alaska. This virus, designated arctic squirrel hepatitis vir us (ASHV), was initially detected in the livers of animals bearing lar ge hepatic nodules by nucleic acid hybridization with hepadnavirus pro bes and in plasma by cross-reactivity with antibodies to hepadnavirus surface and core antigens. The complete nucleotide sequence of the 3,3 02-bp-long ASHV genome was determined and compared with those of groun d squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus (WHV); all sequences were organized into four open reading frames, designate d pre-C/C, Dre-S/S, pol, and X. Despite roughly equivalent variability among the three rodent hepadnaviruses (around 16% base and 19% amino acid exchanges), ASHV appeared to be more closely related to GSHV than to WHV in phylogenetic analysis. Accordingly, preliminary studies of the pathology of ASHV infection suggested that ASHV may. be a less eff icient oncogenic agent than WHV. About one-third of aged animals maint ained in captivity, including virus-infected as well as uninfected squ irrels, developed large liver nodules, consisting of hepatocellular ad enomas or carcinomas or nonmalignant lesions characterized by drastic microvesicular steatosis. ASHV-infected arctic ground squirrels may se rve as a new model with which to analyze the contribution of hepadnavi rus- and host-specific determinants to liver pathology and tumorigenes is.