Neuropathogenicity of mouse hepatitis virus JHM isolates differing in hemagglutinin-esterase protein expression.

K. Yokomori, M. Asanaka, S. A. Stohlman, Shinji Makino, R. A. Shubin, W. Gilmore, L. P. Weiner, F. I. Wang, M. M. Lai

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Abstract

The hemagglutinin-esterase (HE) protein of mouse hepatitis virus (MHV) is an optional envelope protein present in only some MHV isolates. Its expression is regulated by the copy number of a UCUAA pentanucleotide sequence present in the leader sequence of the viral genomic RNA. The functional significance of this viral protein so far is not clear. In this report, we compared the neuropathogenicity of two MHV isolates, JHM(2) and JHM(3), which express different amounts of HE protein. Intracerebral inoculation of these two viruses into C57BL/6 mice showed that JHM(2), which expresses an abundant amount of HE protein, was more neurovirulent than JHM(3), which expresses very little HE. Histopathology showed that early in infection, JHM(2) infected primarily neurons, while JHM(3) infected mainly glial cells. JHM(3) eventually infected neurons and caused a delayed death relative to JHM(2)-infected mice, suggesting that the progression of JHM(3) infection in the central nervous system was slower than JHM(2). In vitro infection of JHM(3) in primary mixed glial cell cultures of astrocyte-enriched cultures yielded higher virus titers than JHM(2), mimicking the preferential growth of JHM(3) in glial cells in vivo. These findings suggest that the reduced neuropathogenicity of JHM(3) may correlate with its preferential growth in glial cells. Sequence analysis showed that the S genes of these two viruses are identical, thus ruling out the S gene as the cause of the difference in neuropathogenicity between these two viruses. We conclude that the HE protein contributes to viral neuropathogenicity by influencing either the rate of virus spread, viral cell tropism or both.

Original languageEnglish (US)
Pages (from-to)330-339
Number of pages10
JournalJournal of NeuroVirology
Volume1
Issue number5-6
StatePublished - Dec 1995
Externally publishedYes

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Murine hepatitis virus
Neuroglia
Viruses
Proteins
Viral Tropism
Neurons
Central Nervous System Infections
Viral RNA
Viral Proteins
Growth
Infection
Viral Load
Inbred C57BL Mouse
Astrocytes
Genes
Sequence Analysis
Cell Culture Techniques
hemagglutinin esterase

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology

Cite this

Yokomori, K., Asanaka, M., Stohlman, S. A., Makino, S., Shubin, R. A., Gilmore, W., ... Lai, M. M. (1995). Neuropathogenicity of mouse hepatitis virus JHM isolates differing in hemagglutinin-esterase protein expression. Journal of NeuroVirology, 1(5-6), 330-339.

Neuropathogenicity of mouse hepatitis virus JHM isolates differing in hemagglutinin-esterase protein expression. / Yokomori, K.; Asanaka, M.; Stohlman, S. A.; Makino, Shinji; Shubin, R. A.; Gilmore, W.; Weiner, L. P.; Wang, F. I.; Lai, M. M.

In: Journal of NeuroVirology, Vol. 1, No. 5-6, 12.1995, p. 330-339.

Research output: Contribution to journalArticle

Yokomori, K, Asanaka, M, Stohlman, SA, Makino, S, Shubin, RA, Gilmore, W, Weiner, LP, Wang, FI & Lai, MM 1995, 'Neuropathogenicity of mouse hepatitis virus JHM isolates differing in hemagglutinin-esterase protein expression.', Journal of NeuroVirology, vol. 1, no. 5-6, pp. 330-339.
Yokomori, K. ; Asanaka, M. ; Stohlman, S. A. ; Makino, Shinji ; Shubin, R. A. ; Gilmore, W. ; Weiner, L. P. ; Wang, F. I. ; Lai, M. M. / Neuropathogenicity of mouse hepatitis virus JHM isolates differing in hemagglutinin-esterase protein expression. In: Journal of NeuroVirology. 1995 ; Vol. 1, No. 5-6. pp. 330-339.
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abstract = "The hemagglutinin-esterase (HE) protein of mouse hepatitis virus (MHV) is an optional envelope protein present in only some MHV isolates. Its expression is regulated by the copy number of a UCUAA pentanucleotide sequence present in the leader sequence of the viral genomic RNA. The functional significance of this viral protein so far is not clear. In this report, we compared the neuropathogenicity of two MHV isolates, JHM(2) and JHM(3), which express different amounts of HE protein. Intracerebral inoculation of these two viruses into C57BL/6 mice showed that JHM(2), which expresses an abundant amount of HE protein, was more neurovirulent than JHM(3), which expresses very little HE. Histopathology showed that early in infection, JHM(2) infected primarily neurons, while JHM(3) infected mainly glial cells. JHM(3) eventually infected neurons and caused a delayed death relative to JHM(2)-infected mice, suggesting that the progression of JHM(3) infection in the central nervous system was slower than JHM(2). In vitro infection of JHM(3) in primary mixed glial cell cultures of astrocyte-enriched cultures yielded higher virus titers than JHM(2), mimicking the preferential growth of JHM(3) in glial cells in vivo. These findings suggest that the reduced neuropathogenicity of JHM(3) may correlate with its preferential growth in glial cells. Sequence analysis showed that the S genes of these two viruses are identical, thus ruling out the S gene as the cause of the difference in neuropathogenicity between these two viruses. We conclude that the HE protein contributes to viral neuropathogenicity by influencing either the rate of virus spread, viral cell tropism or both.",
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AU - Shubin, R. A.

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