Ground Squirrel Hepatitis Virus Infection

Abstract

Twenty-four adult Beechey ground squirrels persistently infected with the hepatitis B virusrelated ground squirrel hepatitis virus (GSHV) remained infected with high levels of viral surface antigen (GSHsAg) and virion-associated DNA polymerase activity in the blood for over 2 years in captivity. Unlike humans infected with hepatitis B virus, no GSHsAg-bearing ground squirrels had surface antigen in the blood without DNA polymerase-containing virions, and the levels of these did not change. Only a very mild hepatitis was observed histologically in some of the virusinfected animals, with faint Shikata-staining detectable in some. Other animals exhibited no histologic evidence of hepatitis. While the closely related woodchuck hepatitis virus has been associated with more severe chronic hepatitis and a high incidence of liver cancer in woodchucks, these were not found in GSHV-infected ground squirrels when a similar number of animals were followed for a similar time of observation. Experimental infection of ground squirrels with no evidence of current or past GSHV infection resulted in three types of response: (i) self-limited or transient GSHV-positive infection; (ii) GSHV-positive infection which became persistent, and (iii) primary anti-GSHs and anti-GSHc (antibody to the viral core antigen) responses without detectable GSHsAg or virion DNA polymerase activity in the blood. These responses are similar to those observed following experimental infection of man with HBV. GSHV produced none of the three responses when injected into a variety of laboratory animal species and a chimpanzee, causing only an antibody response to GSHsAg. No evidence of current or past infection was detected in a number of animal species from an area endemic for GSHV. The virus has only been found in one area of northern California, with a carrier rate in that location reaching 52%.Ground squirrel hepatitis virus (GSHV) is a small hepatotropic DNA virus of the hepadna virus family (l), whose prototype is human hepatitis B virus (HBV). After discovering this virus in Beechey ground squirrels in 1979, we showed that it had the following common features with HBV: virus morphology, virion DNA size and structure, a virion DNA polymerase (DNAp) that repairs a single-stranded region in the viral DNA, cross-reacting viral antigens, and persistent infection with viral antigen continuously in the blood (1). Specific and sensitive assays for both the surface and core antigens (GSHsAg and GSHcAg) of the virus and for the antibodies to these antigens were developed in this laboratory (2-5). The physical properties of the surface antigen particles of GSHV and HBV were analyzed in parallel, showing that the particles have the same buoyant densities and the same pattern of polypeptides, although the two major Received November 26, 1982; accepted February 23, 1983. polypeptides of GSHV migrate faster in SDS polyacrylamide gel electrophoresis than do those of HBV (2, 3). The tryptic peptide map homology between the major nonglycosylated polypeptides of the tw...

Codon usage pattern and its influencing factors in different genomes of hepadnaviruses

“…Chronically infected woodchucks have a high probability of developing hepatocellular carcinoma, although cirrhosis may not occur [2]. Ground squirrel hepatitis virus can also cause hepatitis, and chronically infected animals sometimes develop hepatocellular carcinoma [43]. Infected pekin ducks show few disease symptoms, with noncytopathic replication occurring in hepatocytes [1].…”

Harderian Gland Neoplasms in Captive, Wild-caught Beechey Ground Squirrels (Spermophilus beecheyi)

“…Animals were generally estimated to be 1 or 2 years of age at the time they were captured, based on patterns of tooth wear, unless they were juvenile. 15 Because these animals only breed once a year the ages could be estimated with reasonable accuracy. The average natural life expectancy of the animals in the colony was not known because of periodic euthanasia for experimental studies and a lack of sufficient records.…”

“…14,15 Like chronic HBV infection, which carries a significant risk of hepatocellular carcinoma in humans, 16 GSHV infection is also associated with liver tumor development in chronically infected ground squirrels. 17 Since chronic GSHV infection was a risk factor for tumor formation in one gland, the liver, and other hepatitis viruses such as woodchuck hepatitis virus can replicate in extrahepatic tissues such as the pancreas and lymphoid organs, 18 we evaluated the association between chronic infection and tumor development in the Harderian gland as well.…”

The Laboratory Woodchuck (Marmota monax)

“…These observations suggest that HBV has a direct oncogenic role similar to that of other tumor-producing viruses in which integrated viral DNA or, in the case of retroviruses, proviral DNA causes malignant transformation by insertional mutagenesis (Chen et al, 1982;Shafritz, 1982). At least four members of the family Sciuridae have been described in which persistent hepadnavirus infection has been closely associated with development of HCC (Table 8. 1;Summers et al, 1978;Marion et al, 1983Marion et al, , 1986Testut et al, 1996;and Tennant et al, 2004). At least four members of the family Sciuridae have been described in which persistent hepadnavirus infection has been closely associated with development of HCC (Table 8. 1;Summers et al, 1978;Marion et al, 1983Marion et al, , 1986Testut et al, 1996;and Tennant et al, 2004).…”