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Review

The Challenge of Lyssavirus Infections in Domestic and Other Animals: A Mix of Virological Confusion, Consternation, Chagrin, and Curiosity

by
Charles E. Rupprecht
1,2,*,
Aniruddha V. Belsare
1,2,
Florence Cliquet
3,
Philip P. Mshelbwala
4,
Janine F. R. Seetahal
5 and
Vaughn V. Wicker
6
1
College of Forestry, Wildlife and Environment, Auburn University, Auburn, AL 36849, USA
2
College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA
3
EU/WOAH/WHO Reference Laboratory for Rabies, OMCL for Rabies Vaccines, 54220 Malzéville, France
4
NSW Department of Primary Industries, Orange, NSW 2800, Australia
5
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA
6
Independent Researcher, Atlanta, GA 30307, USA
*
Author to whom correspondence should be addressed.
Pathogens 2025, 14(6), 586; https://doi.org/10.3390/pathogens14060586
Submission received: 6 May 2025 / Revised: 27 May 2025 / Accepted: 28 May 2025 / Published: 13 June 2025
(This article belongs to the Special Issue Current Challenges in Veterinary Virology)

Abstract

Lyssaviruses are RNA viruses in the Family Rhabdoviridae, Genus Lyssavirus. They represent the causative agents of acute, progressive encephalitis, known historically as rabies. Regardless of specific etiology, their collective viral morphology, biochemistry, pathobiology, associated clinical signs, diagnosis, epizootiology, and management are essentially the same. Despite centuries of clinical recognition, these quintessential neurotropic agents remain significant pathogens today, with substantive consequences to agriculture, public health, and conservation biology. Notably, the singular morbidity caused by lyssaviruses is incurable and constitutes the highest case fatality of any viral disease. All warm-blooded vertebrates are believed to be susceptible. The dog is the only domestic animal that serves as a reservoir, vector, and victim. In contrast, felids are effective vectors, but not reservoirs. All other rabid domestic species, such as livestock, constitute spillover infections, as a bellwether to local lyssavirus activity. Frequently, professional confusion abounds among the veterinary community, because although the viral species Lyssavirus rabies is inarguably the best-known representative in the Genus, at least 20 other recognized or putative members of this monophyletic group are known. Frequently, this is simply overlooked. Moreover, often the ‘taxonomic etiology’ (i.e., ‘Lyssavirus x’) is mistakenly referenced in a biopolitcal context, instead of the obvious clinical illness (i.e., ‘rabies’). Global consternation persists, if localities believe they are ‘disease-free’, when documented lyssaviruses circulate or laboratory-based surveillance is inadequate to support such claims. Understandably, professional chagrin develops when individuals mistake the epidemiological terminology of control, prevention, elimination, etc. Management is not simple, given that the only licensed veterinary and human vaccines are against rabies virus, sensu lato. There are no adequate antiviral drugs for any lyssaviruses or cross-reactive biologics developed against more distantly related viral members. While representative taxa among the mammalian Orders Chiroptera, Carnivora, and Primates exemplify the major global reservoirs, which mammalian species are responsible for the perpetuation of other lyssaviruses remains a seemingly academic curiosity. This zoonosis is neglected. Clearly, with such underlying characteristics as a fundamental ‘disease of nature’, rabies, unlike smallpox and rinderpest, is not a candidate for eradication. With the worldwide zeal to drive human fatalities from canine rabies viruses to zero by the rapidly approaching year 2030, enhanced surveillance and greater introspection of the poorly appreciated burden posed by rabies virus and diverse other lyssaviruses may manifest as an epidemiological luxury to the overall global program of the future.
Keywords: challenges; diagnostics; epidemiology; lyssavirus; One Health; rabies; vaccines; veterinary; virology; zoonoses challenges; diagnostics; epidemiology; lyssavirus; One Health; rabies; vaccines; veterinary; virology; zoonoses

Share and Cite

MDPI and ACS Style

Rupprecht, C.E.; Belsare, A.V.; Cliquet, F.; Mshelbwala, P.P.; Seetahal, J.F.R.; Wicker, V.V. The Challenge of Lyssavirus Infections in Domestic and Other Animals: A Mix of Virological Confusion, Consternation, Chagrin, and Curiosity. Pathogens 2025, 14, 586. https://doi.org/10.3390/pathogens14060586

AMA Style

Rupprecht CE, Belsare AV, Cliquet F, Mshelbwala PP, Seetahal JFR, Wicker VV. The Challenge of Lyssavirus Infections in Domestic and Other Animals: A Mix of Virological Confusion, Consternation, Chagrin, and Curiosity. Pathogens. 2025; 14(6):586. https://doi.org/10.3390/pathogens14060586

Chicago/Turabian Style

Rupprecht, Charles E., Aniruddha V. Belsare, Florence Cliquet, Philip P. Mshelbwala, Janine F. R. Seetahal, and Vaughn V. Wicker. 2025. "The Challenge of Lyssavirus Infections in Domestic and Other Animals: A Mix of Virological Confusion, Consternation, Chagrin, and Curiosity" Pathogens 14, no. 6: 586. https://doi.org/10.3390/pathogens14060586

APA Style

Rupprecht, C. E., Belsare, A. V., Cliquet, F., Mshelbwala, P. P., Seetahal, J. F. R., & Wicker, V. V. (2025). The Challenge of Lyssavirus Infections in Domestic and Other Animals: A Mix of Virological Confusion, Consternation, Chagrin, and Curiosity. Pathogens, 14(6), 586. https://doi.org/10.3390/pathogens14060586

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