Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis

S. I. Chowdhury, M. Onderci, P. S. Bhattacharjee, A. Al-Mubarak, M. L. Weiss, You Zhou

Research output: Contribution to journalArticle

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Abstract

Bovine herpesvirus 5 (BHV-5) is a neurovirulent alphaherpesvirus that causes fatal encephalitis in calves. In a rabbit model, the virus invades the central nervous system (CNS) anterogradely from the olfactory mucosa following intranasal infection. In addition to glycoproteins E and I (gE and gI, respectively), Us9 and its homologue in alphaherpesviruses are necessary for the viral anterograde spread from the presynaptic to postsynaptic neurons. The BHV-5 Us9 gene sequence was determined, and the predicted amino acid sequence of BHV-5 Us9 was compared with the corresponding Us9 sequences of BHV-1.1. Alignment results showed that they share 77% identity and 83% similarity. BHV-5 Us9 peptide-specific antibody recognized a doublet of 17 and 19-kDa protein bands in BHV-5 infected cell lysates and in purified virions. To determine the role of the BHV-5 Us9 gene in BHV-5 neuropathogenesis, a BHV-5 Us9 deletion recombinant was generated and its neurovirulence and neuroinvasive properties were compared with those of a Us9 rescue mutant of BHV-5 in a rabbit model. Following intranasal infection, the Us9 rescue mutant of BHV-5 displayed a wild-type level of neurovirulence and neural spread in the olfactory pathway, but the Us9 deletion mutant of BHV-5 was virtually avirulent and failed to invade the CNS. In the olfactory mucosa containing the olfactory receptor neurons, the Us9 deletion mutant virus replicated with an efficiency similar to that of the Us9 rescue mutant of BHV-5. However, the Us9 deletion mutant virus was not transported to the bulb. Confocal microscopy of the olfactory epithelium detected similar amounts of virus-specific antigens in the cell bodies of olfactory receptor neuron for both the viruses, but only the Us9 rescue mutant viral proteins were detected in the processes of the olfactory receptor neurons. When injected directly into the bulb, both viruses were equally neurovirulent, and they were transported retrogradely to areas connected to the bulb. Taken together, these results indicate that Us9 is essential for the anterograde spread of the virus from the olfactory mucosa to the bulb.

Original languageEnglish (US)
Pages (from-to)3839-3851
Number of pages13
JournalJournal of virology
Volume76
Issue number8
DOIs
StatePublished - Apr 6 2002

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Bovine Herpesvirus 5
Bovine herpesvirus 5
Olfactory Mucosa
Viruses
viruses
mutants
Olfactory Receptor Neurons
bulbs
olfactory receptors
neurons
mucosa
central nervous system
Central Nervous System
rabbits
Rabbits
Olfactory Pathways
viral proteins
Viral Proteins
Encephalitis
Mutant Proteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Chowdhury, S. I., Onderci, M., Bhattacharjee, P. S., Al-Mubarak, A., Weiss, M. L., & Zhou, Y. (2002). Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. Journal of virology, 76(8), 3839-3851. https://doi.org/10.1128/JVI.76.8.3839-3851.2002

Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. / Chowdhury, S. I.; Onderci, M.; Bhattacharjee, P. S.; Al-Mubarak, A.; Weiss, M. L.; Zhou, You.

In: Journal of virology, Vol. 76, No. 8, 06.04.2002, p. 3839-3851.

Research output: Contribution to journalArticle

Chowdhury, SI, Onderci, M, Bhattacharjee, PS, Al-Mubarak, A, Weiss, ML & Zhou, Y 2002, 'Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis', Journal of virology, vol. 76, no. 8, pp. 3839-3851. https://doi.org/10.1128/JVI.76.8.3839-3851.2002
Chowdhury SI, Onderci M, Bhattacharjee PS, Al-Mubarak A, Weiss ML, Zhou Y. Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. Journal of virology. 2002 Apr 6;76(8):3839-3851. https://doi.org/10.1128/JVI.76.8.3839-3851.2002
Chowdhury, S. I. ; Onderci, M. ; Bhattacharjee, P. S. ; Al-Mubarak, A. ; Weiss, M. L. ; Zhou, You. / Bovine herpesvirus 5 (BHV-5) Us9 is essential for BHV-5 neuropathogenesis. In: Journal of virology. 2002 ; Vol. 76, No. 8. pp. 3839-3851.
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