Transmission of Ground Squirrel Hepatitis Virus to Homologous and Heterologous Hosts

Trueba, Daniel; Phelan, Michael A.; Nelson, John B.; Beck, Fred; Pecha, B; Brown, Robin; Varmus, Harold; Ganem, M D Don

doi:10.1002/hep.1840050316

Cited by 23 publications

(11 citation statements)

References 13 publications

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“…In 1983 we had detected no liver tumors in infected or uninfected ground squirrels (16). Liver tumors were also not noted in another large colony of Beechey ground squirrels (17). The failure to observe HCC in GSHVinfected ground squirrels has contrasted sharply with the observations in WHV-infected woodchucks and has raised the question of whether such tumors ever arise in GSHVinfected animals.…”

mentioning

confidence: 84%

Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.

Marion¹,

Davelaar²,

Knight³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

120

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Although persistent infection with hepatitis B virus and woodchuck hepatitis virus has been associated with development of hepatocellular carcinoma in the host, little has been known of such an association with ground squirrel hepatitis virus (GSHV), which is closely related to the woodchuck virus. Colonies of GSHV-infected and -uninfected Beechey ground squirrels were observed for tumors for a period of 5 years. Tumors developed in seven squirrels after a minimum of 2.4 years of observation per animal; each of the seven animals was over 4 years old when the tumor was detected. The predominant type of tumor was hepatocellular carcinoma, which appeared in 2 of 28 GSHV-bearing animals studied and in 1 of 23 squirrels with antibody to the virus. No

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mentioning

confidence: 84%

Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.

Marion¹,

Davelaar²,

Knight³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

120

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“…In most cases transmission of virus to hosts closely related to the natural host species is demonstrable: HBV will replicate in several nonhuman primate sp ecies (16); GSHV infection has been successfully transmitted to chipmunks (62) and woodchucks (C. Seeger, D. Ganem Much interest is now focused on determining the pathologic consequences of infection with the animal hepadnav iru ses. The picture is most clear for WHV, since severe chronic hepatitis and hepatoma are fr equent in naturally infected populations (49).…”

Section: Animal Hepadnavirusesmentioning

confidence: 99%

The Molecular Biology of the Hepatitis B Viruses

Ganem¹,

Varmus²

1987

Annu. Rev. Biochem.

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1,014

591

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“…HBV can be transmitted to chimpanzees [14] but not [15], or only extremely inefficiently [16], to baboons; WHV was not infectious for ground squirrels [17]; and DHBV does not infect chicken [18]. Notably, though, this barrier is not absolute; for instance, Beechey Ground Squirrel HBV (GSHV) was infectious for woodchucks and chipmunks [19], though not mice or rats [20]. In vitro, host tropism appears more relaxed as shown by the relatively efficient infectibility of tupaia hepatocytes [10],[11] by HBV and woolly monkey HBV (WMHBV; [21]), or of duck hepatocytes by crane hepatitis B virus [22].…”

Section: Introductionmentioning

confidence: 99%

Heterologous Replacement of the Supposed Host Determining Region of Avihepadnaviruses: High In Vivo Infectivity Despite Low Infectivity for Hepatocytes

Dallmeier

Schultz²,

Nassal³

2008

PLoS Pathog

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Hepadnaviruses, including hepatitis B virus (HBV), a highly relevant human pathogen, are small enveloped DNA viruses that replicate via reverse transcription. All hepadnaviruses display a narrow tissue and host tropism. For HBV, this restricts efficient experimental in vivo infection to chimpanzees. While the cellular factors mediating infection are largely unknown, the large viral envelope protein (L) plays a pivotal role for infectivity. Furthermore, certain segments of the PreS domain of L from duck HBV (DHBV) enhanced infectivity for cultured duck hepatocytes of pseudotyped heron HBV (HHBV), a virus unable to infect ducks in vivo. This implied a crucial role for the PreS sequence from amino acid 22 to 90 in the duck tropism of DHBV. Reasoning that reciprocal replacements would reduce infectivity for ducks, we generated spreading-competent chimeric DHBVs with L proteins in which segments 22–90 (Du-He4) or its subsegments 22–37 and 37–90 (Du-He2, Du-He3) are derived from HHBV. Infectivity for duck hepatocytes of Du-He4 and Du-He3, though not Du-He2, was indeed clearly reduced compared to wild-type DHBV. Surprisingly, however, in ducks even Du-He4 caused high-titered, persistent, horizontally and vertically transmissable infections, with kinetics of viral spread similar to those of DHBV when inoculated at doses of 108 viral genome equivalents (vge) per animal. Low-dose infections down to 300 vge per duck did not reveal a significant reduction in specific infectivity of the chimera. Hence, sequence alterations in PreS that limited infectivity in vitro did not do so in vivo. These data reveal a much more complex correlation between PreS sequence and host specificity than might have been anticipated; more generally, they question the value of cultured hepatocytes for reliably predicting in vivo infectivity of avian and, by inference, mammalian hepadnaviruses, with potential implications for the risk assessment of vaccine and drug resistant HBV variants.

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Transmission of Ground Squirrel Hepatitis Virus to Homologous and Heterologous Hosts

Cited by 23 publications

References 13 publications

Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.

Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.

The Molecular Biology of the Hepatitis B Viruses

Heterologous Replacement of the Supposed Host Determining Region of Avihepadnaviruses: High In Vivo Infectivity Despite Low Infectivity for Hepatocytes

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