Viral Zoonoses

Human infection by zoonotic viruses—pathogens that normally infect animals—may result in no obvious illness, a nonspecific viral syndrome, or more severe illness typically characterized by hemorrhagic fever, encephalitis, or rash arthralgia. Transmission usually occurs by direct contact with or a bite from an infected animal or arthropod. Viral families discussed include Flaviviridae, Bunyaviridae, Arenaviridae, Filoviridae, Togaviridae, Rhabdoviridae, Paramyxoviridae, and Reoviridae, with consideration given to the epidemiology, diagnosis, treatment, and prevention of specific viruses. Hemorrhagic fevers addressed include dengue fever, dengue hemorrhagic fever, yellow fever, Crimean-Congo hemorrhagic fever, and Rift Valley fever; hantavirus infections; and the Marburg and Ebola viruses. Encephalitic fever–causing viruses discussed include La Crosse; Japanese; Murray Valley; St. Louis; tick-borne; West Nile; Powassan; eastern, western, and Venezuelan equine; rabies; Nipah; Barmah Forest; and Colorado tick fever. Rash arthralgia may be caused by the Barmah Forest, Chikungunya, Mayaro, O’nyong-nyong, Ross River, and dengue viruses. Other viral zoonoses considered include monkey B virus, ruminant and primate poxvirus, Newcastle, and foot-and-mouth diseases, as well as vesicular stomatitis virus infection. A diagram depicts the generalized arbovirus maintenance cycle. Tables list the important viral zoonoses that cause human disease, the principal hantaviruses that cause human disease, the arenaviruses that cause significant human illness, and the viral zoonoses endemic in the United States. This review contains 1 figure, 32 tables, and 80 references. Key words: dengue, diagnosis, encephalitis, epidemic, epidemiology, infection, rabies, virus, vaccine

Effective Prophylactic Therapy for Exposure to Monkey B Virus (Macacine alphaherpesvirus 1)

Zoonotic monkey B virus (Macacine alphaherpesvirus 1; BV) infections are extremely serious and usually fatal. Drugs currently used for treatment were developed for the treatment of herpes simplex virus but are less effective against BV. Effective suppression of viral replication in the skin could prevent the virus from invading the nervous system. To test this hypothesis, the efficacy of topical administration of several drugs against lethal BV infection was evaluated in female BALB/c mice that were infected by scarification. Drugs were then applied to the site of inoculation. As 3% preparations, most drugs were only minimally effective or ineffective. In contrast, ganciclovir and cidofovir were very effective. The ED50 for cidofovir was 0.007%, compared with 1.1% for ganciclovir. At 0.5%, cidofovir protected against both death and neurologic signs, whereas 5% ganciclovir only protected against death but not neurologic involvement. All genotypes of BV were equally susceptible to cidofovir and ganciclovir. For maximal effectiveness, treatment with both cidofovir and ganciclovir had to be initiated within 8 h of infection. Cidofovir was completely protective when administered only on the day of infection, whereas a minimum of 5 d of treatment was required for maximal ganciclovir efficacy. These studies showed that topical cidofovir treatment started soon after BV exposure was very effective in preventing BV from invading the nervous system, whereas ganciclovir treatment was only partially effective. In addition, cidofovir was protective against a ganciclovir-resistant BV mutant, whereas ganciclovir was not. These studies showed that topical cidofovir treatment started soon after BV exposure is more effective than ganciclovir in preventing BV from invading the CNS.

Questioning the Extreme Neurovirulence of Monkey B Virus(Macacine alphaherpesvirus 1)

Monkey B virus (Macacine alphaherpesvirus1; BV) occurs naturally in macaques of the genusMacaca,which includes rhesus and long-tailed (cynomolgus) monkeys that are widely used in biomedical research. BV is closely related to the human herpes simplex viruses (HSV), and BV infections in its natural macaque host are quite similar to HSV infections in humans. Zoonotic BV is extremely rare, having been diagnosed in only a handful of North American facilities with the last documented case occurring in 1998. However, BV is notorious for its neurovirulence since zoonotic infections are serious, usually involving the central nervous system, and are frequently fatal. Little is known about factors underlying the extreme neurovirulence of BV in humans. Here we review what is actually known about the molecular biology of BV and viral factors affecting its neurovirulence. Based on what is known about related herpesviruses, areas for future research that may elucidate mechanisms underlying the neurovirulence of this intriguing virus are also reviewed.