A new hepadnavirus endemic in arctic ground squirrels in Alaska

Abstract

We present evidence for a novel member of the hepadnavirus family that is endemic in wild arctic ground squirrels (Spermophylus parryi kennicotti) in Alaska. This virus, designated arctic squirrel hepatitis virus (ASHV), was initially detected in the livers of animals bearing large hepatic nodules by nucleic acid hybridization with hepadnavirus probes and in plasma by cross-reactivity with antibodies to hepadnavirus surface and core antigens. The complete nucleotide sequence of the 3,302-bp-long ASHV genome was determined and compared with those of ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus (WHV); all sequences were organized into four open reading frames, designated pre-C/C, pre-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 efficient oncogenic agent than WHV. About one-third of aged animals maintained in captivity, including virus-infected as well as uninfected squirrels, developed large liver nodules, consisting of hepatocellular adenomas or carcinomas or nonmalignant lesions characterized by drastic microvesicular steatosis. ASHVinfected arctic ground squirrels may serve as a new model with which to analyze the contribution of hepadnavirus-and host-specific determinants to liver pathology and tumorigenesis.

Extensive diversity and evolution of hepadnaviruses in bats in China

“…Hence, combined with previous studies, these data indicate that bats are an important natural reservoir of orthohepadnaviruses. Although rodents comprise the largest order of mammals (Wilson and Reeder, 2005) and are a major source of zoonotic infectious diseases (Meerburg et al, 2009;Han et al, 2015), to date hepadnaviruses have only been discovered in three species of ground squirrels in the USA (Summers et al, 1978;Marion et al, 1980;Testut et al, 1996). We surveyed 462 rodents from 8 species and 148 Asian house shrews from Zhejiang province.…”

“…Orthohepadnaviruses infect mammals including humans. Although hepadnaviruses were discovered in ground squirrels (genus Marmota) in the USA (Summers et al, 1978;Marion et al, 1980;Testut et al, 1996), they have been not observed in other rodents or in other geographic localities. Notably, however, orthohepadnaviruses have recently been identified in both Old and New World bats: specifically, long-fingered bat HBV (LBHBV) in Miniopterus fuliginosus from Myanmar (He et al, 2013), tent-making bat hepatitis B virus (TBHBV) in Uroderma bilobatum from Panama, roundleaf bat HBV (RBHBV) and horseshoe bat HBV (HBHBV) in Hipposideros cf.…”

Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region

“…This affects the ORF for HBcAg (cD153 and cR154), but not hepatitis B e antigen (HBeAg) (not shown), because this length polymorphism is located immediately carboxyterminal of the HBeAg processing site. None of the other human or ape HBV genotypes have this 2 amino acid insertion, but remarkably, there is a 5 amino acid insertion present at the same position in rodent hepadnaviruses (woodchuck hepatitis virus, 59 Arctic ground squirrel hepatitis virus, 60 and ground squirrel hepatitis virus 61 ; not shown). Because the efficiency of the backwards scanning mechanism depends on the distance between the 3Ј end of the core ORF and initiation of the polymerase ORF 43 (143 nucleotides for genotype B-G, 149 for genotype A, 158 for rodent hepatitis viruses), these length polymorphisms might help control the translation of the polymerase protein from the pregenomic mRNA in a genotype-dependent manner.…”

Evolutionary biology of human hepatitis viruses

“…Chronic courses of hepadnavirus infections also occur in ducks, squirrels, and NHPs (Table 2). 30,96,112,113,[116][117][118]153 Whether chronic hepadnavirus infections occur in bats is unclear. 30 Among non-human hepaciviruses, studies reporting chronic infections are scarce.…”