Genomic heterogeneity among human and nonhuman strains of hepatitis A virus

S. M. Lemon, S. F. Chao, R. W. Jansen, L. N. Binn, James LeDuc

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Cloned cDNA probes derived from the P1 and P2 regions of the genome of HM175 virus, a reference strain of human hepatitis A virus (HAV), failed to hybridize under standard stringency criteria with RNA from PA21 and PA33 viruses, two epizootiologically related HAV strains recovered from naturally infected New World owl monkeys. Hybridization of these probes to PA21 RNA was only evident under reduced stringency conditions. However, cDNA representing the 5' nontranslated region of the HM175 genome hybridized equally to HM175 and PA21 RNA under standard stringency conditions, while a probe derived from the 3' 1,400 bases of the genome yielded a reduced hybridization signal with PA21 RNA. In contrast, no differences could be discerned between HM175 virus and three other HAV strains of human origin (GR8, LV374, and MS1) in any region of the genome, unless increased stringency conditions were used. These results suggest that PA21 and PA33 are unique among HAV isolates and may represent a virus native to the owl monkey. Despite extremely poor homology within the P1 region, which encodes capsid polypeptides, monoclonal antibody analysis confirmed that the immunodominant neutralization epitopes of HAV were highly conserved between HM175 and PA21 viruses. Furthermore, experimental challenge of the owl monkey with successive PA33 and HM175 inocula confirmed a high but incomplete degree of cross-protection. Only one of six monkeys previously infected with PA33 developed recurrent hepatitis 28 days after intravenous HM175 challenge, while none of six monkeys previously infected with HM175 had demonstrable hepatitis following PA33 challenge. These data provide molecular evidence for the existence of HAV strains unique to nonhuman primate species and indicate that strict conservation of antigenic function may accompany substantial genetic divergence in HAV.

Original languageEnglish (US)
Pages (from-to)735-742
Number of pages8
JournalJournal of Virology
Volume61
Issue number3
StatePublished - 1987
Externally publishedYes

Fingerprint

Hepatitis A virus
Aotidae
Human hepatitis A virus
Viruses
genomics
Genome
Aotus (Cebidae)
RNA
viruses
Hepatitis
Haplorhini
genome
Complementary DNA
hepatitis
Platyrrhini
Cross Protection
monkeys
Immunodominant Epitopes
Capsid
Primates

ASJC Scopus subject areas

  • Immunology

Cite this

Lemon, S. M., Chao, S. F., Jansen, R. W., Binn, L. N., & LeDuc, J. (1987). Genomic heterogeneity among human and nonhuman strains of hepatitis A virus. Journal of Virology, 61(3), 735-742.

Genomic heterogeneity among human and nonhuman strains of hepatitis A virus. / Lemon, S. M.; Chao, S. F.; Jansen, R. W.; Binn, L. N.; LeDuc, James.

In: Journal of Virology, Vol. 61, No. 3, 1987, p. 735-742.

Research output: Contribution to journalArticle

Lemon, SM, Chao, SF, Jansen, RW, Binn, LN & LeDuc, J 1987, 'Genomic heterogeneity among human and nonhuman strains of hepatitis A virus', Journal of Virology, vol. 61, no. 3, pp. 735-742.
Lemon, S. M. ; Chao, S. F. ; Jansen, R. W. ; Binn, L. N. ; LeDuc, James. / Genomic heterogeneity among human and nonhuman strains of hepatitis A virus. In: Journal of Virology. 1987 ; Vol. 61, No. 3. pp. 735-742.
@article{18831aa6748645acb182ecd90dc105cc,
title = "Genomic heterogeneity among human and nonhuman strains of hepatitis A virus",
abstract = "Cloned cDNA probes derived from the P1 and P2 regions of the genome of HM175 virus, a reference strain of human hepatitis A virus (HAV), failed to hybridize under standard stringency criteria with RNA from PA21 and PA33 viruses, two epizootiologically related HAV strains recovered from naturally infected New World owl monkeys. Hybridization of these probes to PA21 RNA was only evident under reduced stringency conditions. However, cDNA representing the 5' nontranslated region of the HM175 genome hybridized equally to HM175 and PA21 RNA under standard stringency conditions, while a probe derived from the 3' 1,400 bases of the genome yielded a reduced hybridization signal with PA21 RNA. In contrast, no differences could be discerned between HM175 virus and three other HAV strains of human origin (GR8, LV374, and MS1) in any region of the genome, unless increased stringency conditions were used. These results suggest that PA21 and PA33 are unique among HAV isolates and may represent a virus native to the owl monkey. Despite extremely poor homology within the P1 region, which encodes capsid polypeptides, monoclonal antibody analysis confirmed that the immunodominant neutralization epitopes of HAV were highly conserved between HM175 and PA21 viruses. Furthermore, experimental challenge of the owl monkey with successive PA33 and HM175 inocula confirmed a high but incomplete degree of cross-protection. Only one of six monkeys previously infected with PA33 developed recurrent hepatitis 28 days after intravenous HM175 challenge, while none of six monkeys previously infected with HM175 had demonstrable hepatitis following PA33 challenge. These data provide molecular evidence for the existence of HAV strains unique to nonhuman primate species and indicate that strict conservation of antigenic function may accompany substantial genetic divergence in HAV.",
author = "Lemon, {S. M.} and Chao, {S. F.} and Jansen, {R. W.} and Binn, {L. N.} and James LeDuc",
year = "1987",
language = "English (US)",
volume = "61",
pages = "735--742",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "3",

}

TY - JOUR

T1 - Genomic heterogeneity among human and nonhuman strains of hepatitis A virus

AU - Lemon, S. M.

AU - Chao, S. F.

AU - Jansen, R. W.

AU - Binn, L. N.

AU - LeDuc, James

PY - 1987

Y1 - 1987

N2 - Cloned cDNA probes derived from the P1 and P2 regions of the genome of HM175 virus, a reference strain of human hepatitis A virus (HAV), failed to hybridize under standard stringency criteria with RNA from PA21 and PA33 viruses, two epizootiologically related HAV strains recovered from naturally infected New World owl monkeys. Hybridization of these probes to PA21 RNA was only evident under reduced stringency conditions. However, cDNA representing the 5' nontranslated region of the HM175 genome hybridized equally to HM175 and PA21 RNA under standard stringency conditions, while a probe derived from the 3' 1,400 bases of the genome yielded a reduced hybridization signal with PA21 RNA. In contrast, no differences could be discerned between HM175 virus and three other HAV strains of human origin (GR8, LV374, and MS1) in any region of the genome, unless increased stringency conditions were used. These results suggest that PA21 and PA33 are unique among HAV isolates and may represent a virus native to the owl monkey. Despite extremely poor homology within the P1 region, which encodes capsid polypeptides, monoclonal antibody analysis confirmed that the immunodominant neutralization epitopes of HAV were highly conserved between HM175 and PA21 viruses. Furthermore, experimental challenge of the owl monkey with successive PA33 and HM175 inocula confirmed a high but incomplete degree of cross-protection. Only one of six monkeys previously infected with PA33 developed recurrent hepatitis 28 days after intravenous HM175 challenge, while none of six monkeys previously infected with HM175 had demonstrable hepatitis following PA33 challenge. These data provide molecular evidence for the existence of HAV strains unique to nonhuman primate species and indicate that strict conservation of antigenic function may accompany substantial genetic divergence in HAV.

AB - Cloned cDNA probes derived from the P1 and P2 regions of the genome of HM175 virus, a reference strain of human hepatitis A virus (HAV), failed to hybridize under standard stringency criteria with RNA from PA21 and PA33 viruses, two epizootiologically related HAV strains recovered from naturally infected New World owl monkeys. Hybridization of these probes to PA21 RNA was only evident under reduced stringency conditions. However, cDNA representing the 5' nontranslated region of the HM175 genome hybridized equally to HM175 and PA21 RNA under standard stringency conditions, while a probe derived from the 3' 1,400 bases of the genome yielded a reduced hybridization signal with PA21 RNA. In contrast, no differences could be discerned between HM175 virus and three other HAV strains of human origin (GR8, LV374, and MS1) in any region of the genome, unless increased stringency conditions were used. These results suggest that PA21 and PA33 are unique among HAV isolates and may represent a virus native to the owl monkey. Despite extremely poor homology within the P1 region, which encodes capsid polypeptides, monoclonal antibody analysis confirmed that the immunodominant neutralization epitopes of HAV were highly conserved between HM175 and PA21 viruses. Furthermore, experimental challenge of the owl monkey with successive PA33 and HM175 inocula confirmed a high but incomplete degree of cross-protection. Only one of six monkeys previously infected with PA33 developed recurrent hepatitis 28 days after intravenous HM175 challenge, while none of six monkeys previously infected with HM175 had demonstrable hepatitis following PA33 challenge. These data provide molecular evidence for the existence of HAV strains unique to nonhuman primate species and indicate that strict conservation of antigenic function may accompany substantial genetic divergence in HAV.

UR - http://www.scopus.com/inward/record.url?scp=0023098629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023098629&partnerID=8YFLogxK

M3 - Article

C2 - 2433467

AN - SCOPUS:0023098629

VL - 61

SP - 735

EP - 742

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 3

ER -