Rhabdoviridae

Chapter 63


Rhabdoviridae


Rhabdoviruses are named from the Greek word rhabdos meaning rod which refers to their distinctive morphology. The family Rhabdoviridae along with the families Paramyxoviridae, Bornaviridae and Filoviridae is part of the order Mononegavirales. Viruses within this order possess a linear non-segmented RNA genome of negative polarity in a helical ribonucleoprotein complex (RNP). Rhabdoviruses are enveloped and variable in length, 100–430 nm, and diameter, 45–100 nm. The animal viruses are bullet-shaped while plant rhabdoviruses may be bacilliform- or bullet-shaped (Fig. 63.1). It is a large family comprising six genera Vesiculovirus, Lyssavirus, Ephemerovirus, Novirhabdovirus, Cytorhabdovirus and Nucleorhabdovirus (Fig. 63.2). In addition there are a large number of rhabdoviruses which have not been assigned to any genus yet. Members of the family infect vertebrates, invertebrates and plants. The genera Vesiculovirus, Lyssavirus and Ephemerovirus contain viruses of vertebrates. The genus Novirhabdovirus contains infectious haematopoietic necrosis virus and related rhabdoviruses of fish.




Rhabdoviruses generally contain five structural proteins; ‘large’ protein that is responsible for RNA-dependent RNA polymerase (L), surface glycoprotein (G), nucleoprotein (N), co-factor of the viral polymerase (P) and matrix protein (M). The G protein forms surface peplomers which are responsible for binding to host cell receptors, resulting in endocytosis, and the subsequent fusion of the viral envelope and cell membrane as the pH decreases within the endosome. In addition the G protein induces virus-neutralizing antibodies and elicits cell-mediated immunity. The nucleoprotein has epitopes involved in inducing cell-mediated immunity. Replication occurs in the cytoplasm (with the exception of nucleorhabdoviruses) with budding of the newly synthesized nucleocapsids of animal rhabdoviruses from the plasma membrane. Rhabdoviruses are stable over a pH range of five to 10 but are rapidly inactivated at 56°C and by exposure to lipid solvents or UV light.


The family contains more than 150 viruses of vertebrates, invertebrates and plants, of which a number are of veterinary significance (Table 63.1). Transmission of rhabdoviruses frequently involves an arthropod vector. Arthropods are thought to be the original reservoir hosts from which adaptation to plants and vertebrates occurred. Transmission between vertebrate hosts can also occur by contact, aerosol, bite or venereally. The best known and most important member of the family is rabies virus which is a member of the genus Lyssavirus. The name of the genus is derived from the Greek word lyssa meaning rage or fury. More than 25 viruses isolated from vertebrates and invertebrates have been described in the genus Vesiculovirus. Several vesiculoviruses are known to infect domestic animals, of most importance are vesicular stomatitis Indiana virus (VSIV) and vesicular stomatitis New Jersey virus (VSNJV). Infection of man with these viruses is reasonably common and results in an influenza-like condition. Bovine ephemeral fever or three-day sickness is caused by bovine ephemeral fever virus, the type species of the genus Ephemerovirus. Rhabdoviruses are important causes of disease in fish including infectious haematopoietic necrosis virus, viral haemorrhagic septicaemia virus, eel rhabdovirus, pike fry rhabdovirus and spring viraemia of carp virus. A number of these viruses are members of the genus Vesiculovirus while others have been assigned to the genus Novirhabdovirus.




Rabies


Rabies is a viral infection of the CNS of warm-blooded animals, including man, that usually ends in death of the host. The disease occurs in most parts of the world. All mammals are considered susceptible to infection. The vast majority of clinical cases are due to infection with rabies virus. Several genotypically distinct lyssaviruses are capable of producing rabies-like encephalitis but incidences of human disease due to these ‘rabies-related’ viruses are rare. Antigenic and genetic sequencing studies have allowed the differentiation of at least four serotypes and seven genotypes (Smith 1996, Gould et al. 1998, Marston et al. 2012). The genotypes are sufficiently different to be ascribed separate species status (Table 63.2). An additional five lysssaviruses have been isolated from a number of bat species and classified; West Caucasian bat virus, Shimoni bat virus, Aravan virus, Irkut virus and Khujand virus. Two further lyssaviruses, one from a bat (Bokeloh bat virus) and one from an African civet (Ikoma lyssavirus) have been detected (Marston et al. 2012).



All warm-blooded animals are susceptible to infection with rabies virus. However, there is species variation in susceptibility and several species-adapted variants of rabies virus occur. Each variant is more readily transmitted to members of the same species than to individual animals of a different species. In a particular geographical area rabies virus is usually maintained and transmitted by one or possibly two mammalian species. These species serve as reservoirs and vectors of the infection. Two important epidemiological cycles are recognized, canine (urban) rabies and sylvatic rabies. Canine rabies involves stray dogs and accounts for more than 95% of human cases in developing countries. Sylvatic rabies involves a range of wildlife species, principally small to medium-sized carnivores, that varies geographically and includes foxes, coyotes, racoons, skunks, jackals, mongooses and bats. Rabies virus exploits a number of traits common to these reservoir hosts including the fact that they often live at high population densities and have high intrinsic population growth rates which permit the rapid recovery of a population following a rabies epizootic. In Africa, Asia, South America and the Middle East canine rabies is important whereas in developed countries vaccination and the control of strays have reduced its importance but increased awareness of wildlife reservoirs. In North America racoons, skunks, foxes and bats act as important reservoirs (Krebs et al. 1998). In Europe, the principal reservoir is the red fox. The vampire bat is an important reservoir in Central and South America. In Africa, the predominant rabies virus variants are the mongoose and canine biotypes.


Domestic animals and man are considered to be moderately susceptible to the virus while red foxes, wolves, coyotes and jackals are very susceptible. However, the variant involved in the infection is important in determining the development of disease. Transmission usually occurs through biting. Most infected animals excrete virus in their saliva, beginning a number of days before the onset of clinical signs. The virus may be widely disseminated through social grooming or aggressive encounters. Less common routes of transmission include scratching, licking or aerosol.



Pathogenesis


The incubation period is extremely variable, ranging from a few days to many months. Factors influencing its length include host species, virus strain, amount of inoculum and site of inoculation. Following subdermal inoculation the virus enters peripheral, unmyelinated nerve terminals at the site either immediately or following local replication in non-nervous tissue. The virus is transported to the CNS by retrograde axoplasmic flow. Within the CNS the virus becomes widely disseminated through intra-axonal spread. Clinical signs become apparent at this stage due to cell damage within the CNS caused by the multiplying virus. Subsequently the virus spreads centrifugally to peripheral sites within nerve cells. The virus is released from axon terminals and infects adjacent non-nervous tissue. Most tissues become infected, the most important being the salivary glands. Stimulation of an immune response is minimal due to the highly neurotropic nature of the virus which remains largely protected from immune cells. Neither antibody or virus is readily detectable until after the onset of clinical disease. The clinical course typically lasts from a few days to a few weeks and can be divided into three phases or forms; prodromal, furious (excitative) and paralytic (dumb). Death is usually due to respiratory failure.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Rhabdoviridae

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