CHAPTER 46 THE RHABDOVIRUS, REOVIRUS, AND OTHER RNA VIRUS FAMILIES

THE RHABDOVIRUS FAMILY The only medically important species of rhabdovirus in the united states is the rebiesvirus. Rabies is rare among humans in the united states, there are less than 2 confirmed cases per year since 1980. But animal rabies is still quite prevalent. About 5000 cases were reported in 1987 in the united states. Since rabies is transmitted by animal bites and is uniformly fatal and since post exposure immunoprophylaxis is quite effective, the possibility of exposure to the rabiesvirus must be considered by the attending physician in every instance of animal bite. Because human rabies is extremely rare in the united states, the diagnosis is difficult especially in the absense of an exposure history. It is important to consider rabies the differential diagnosis of acute encephalitis FAMILY CHARACTERISTICS Morphology Rhabdoviruses are enveloped and have helical capsid symmetry. These viruses have a bullet-shaped morphology that is unique for this family. Genomic Chemistry The genome ois a single-stranded negative-sense RNA. Replication Strategy This virus is presumed to be similar to all other enveloped virions with negative-sense RNA genome. The synthetic phase is initiated by a virion-associated polymerase that transcribes the negative-sense into positive-sense RNA(mRNA) Species There are numerous isolates of rhabdoviruses, many of which have not been sufficiently characterized for classification. Only one species the rabiesvirus is important medically in the united states. There is only one immunotype of rabiesvirus (i e vaccine prepared from a standard strain induces immunity against all others). By antigenic analysis

with monoclonal antibodies, several antigenie variants have been identified. Knowledge of these antigenic variants are useful in epidemiology. The rabiesvirus is also known as lyssavirus serotype 1.

RABIESVIRUS Pathogenesis The rabiesvirus enters the human body through the bite of rabid animals. The virus multiplies in muscle cells at the site of inoculation and then enters the nervous system by way of the myoneural junction. In the CNS, the virus multiplies extensively and then descends to the peripheral organs through peripheral nerves. The acetylcholine receptor may serve as a receptor for the virus. The host`s immune response is intimately associated with symptomatology of rabies. The main pathology is acute encephalitis. The incubation period is usually 20-60 days but may be less than 10 days to over 1 year. It is not clear why the incubation period varies so widely.

Diagnosis In the management of animal bites. It is crucial to know if the biting animal is rabid. The method of choice is to detect rabies antigens in the brain smear of the suspected animal by immunofluorescence. As mentioned in chapter 45, entiologic diagnosis of all cases of acute encephalitis must be attempted. The demonstration of rabies antibody is the method of choice patients not previously given rabies immunoprophylaxis.

Treatment Specific antiviral treatment for rabies is not available.

Epidemiology and prevention An epidemiologically important source of rabiesvirus is the saliva of infected animals. Distribution of 4729 repoted cases of rabies among animal species in the united states in 1987 is shown in figure 46.2. key points to note are (1) skunks, raccoons, foxes and bats accounted for 87% (2) dogs and cats only 7% and (3) none among small agile mammals such as mice, chipmunks, squirrels and rabbits. In many developing countries most of the animal rabies are among dogs. For example in 1987 there were about 15.000 reported cases of dog rabies in mexico a number about 30 times higher than in the united states. Prevention of rabies in humans is achieved by (1) mandatory immunization of dogs and cats (2) preexposure immunization of persons at high risk of animal bites (e.g veterinarians,park rangers,animal handlers, etc ) and (3) postexposure immunoprophylaxis of persons exposed to rabies. Postexposure immunoprophylaxis consists of the local infiltration and parenteral administration of human rabies immunoglobulins and a course of rabies vaccine. Rabies vaccine for human use contains inactivated rabiesvirus. The alum-adsorbed type induces acceptable level of rabies neutralizing antibody in over 99% of the vaccinated persons. THE REOVIRUS FAMILY Viruses of this family are unique in that their genomes consist of double stranded RNA. There are many species in this family, but only the rotaviruses produce significant

human diseases in the united states. The rotavirus is a major cause of diarrhea among infants and young children. A specific prevention or treatment for rotavirus diarrhea is not available. FAMILY CHARACTERISTICS Morphology The virion is not enveloped, it has double layers of capsids that are icosahedral in symmetry. The arrangement of capsomeres gives the virion a wheel like appearance that is especially striking for the genus rotavirus. Genomic Chemistry The genome consists of segmented double-stranded RNA. Replication Strategy The virion contains a polymerase that initiates the synthetic by transcribing the viral genome into viral mRNA.

Species Reoviruses are divided into several genera. Three are pathogenic to humans found in the united states. The three genera are reovirus, rotavirus and orbivirus. Species of the genus reovirus induce minor illnesses or subclinical infections. Colorado tick fever virus (an orbivirus) infections of humans are uncommon. Only species of the genus rotavirus are important in medical practice in the united states. ROTAVIRUS

Pathogenesis The primary target is intestinal epithelial cells. Virus multiplication damages the epithelial lining resulting in watery diarrhea, which can lead to dehydration in infants. Diagnosis Rotavirus is present in high concentration in feces. Virions or viral antigens in feces can be readily by electron microscopy or serology. Ethiologic diagnosis is seldom necessary in medical practise. Treatment There is no specific antiviral treatment Epidemiology and prevention The source of the virus is the feces of infected persons. Transmission is through the fecal-oral route. Rotavirus infections are common. In the united states, over 90% of preschool children have rotavirus antibody and rotavirus diarrhea usually occurs among infants in the winter. There are fiur major serotypes of human rotaviruses. Recovery from infection by one type provides partial immunity against reinfection by the same type. Nesocomial infections among infants are not uncommon. Such infections should be minimized by attending to procedures that prevent fecal-oral transmission. OTHER RNA VIRUS FAMILIES This subchapter deals with the remaining five families of RNA viruses. These viruses are relatively unimportant because they cause self-limiting diseases against which there is no effective preventive or specific treatment or because infections are rare in the united states. THE BUNYAVIRUS FAMILY The bunyavirus family includes over 200 species most of which are arboviruses. Only two species, the LaCrosse encephalitis virus and hantavirus are of medical importance in the united states. Like other arboviruses, LaCrosse virus is transmitted from its nonhuman vertebrate hosts (small mammals and birds) to human by the bites of mosquitoes. LaCrosse encephalitis is an uncommon disease in the united states, it occurs chiefly in the states bordering the dreat lakes.

The hantavirus infects primarily rodents and is found in the excreta of infected rotedents. Humans in close contact with infected rodents acquire infections through the respiratory tract. Severe infections, known as hantavirus pulmonary syndrome, have occurred in western united states and florida and have a mortality of over 50%. Serologic surveys reveal a seroprevalence of 1% in some parts of the united states. In some other countries, severe infections may manifest as hemorrhagis fever with renal syndrome. THE CORONAVIRUS FAMILY Coronaviruses are one of the several groups of viruses capable of causing acute respiratory infections in humans. Specific virologic diagnosis is unnecessary. Effective vaccine and antiviral against the coronavirus are not available. THE CALICIVIRUS FAMILY Calicivirus are one of the several groups of viruses capable of causing acute gastroenteritis in humans. Specific virologic diagnosis is unnecessary. There are no effective vaccines or antiviral agents againts this family of viruses. THE ARENAVIRUS FAMILY Lymphocytic choriomeningitis virus (LCMV) is the only arenavirus of medical importance in the united states. This virus is one of the many viruses capable of causing aseptic meningitis or meningoencephalitis in humans. The LCMV induced meningitis or meningoencephalitis are usually self-limiting and are rare in the united states. There are no effective vaccines or antiviral agents againts LCMV. Infection by LCMV occurs through contact with urine of infected rotents. Lassa fever virus infections are endemic in tropical west africa, imported cases have been reported from the united states and other countries. Lassa fever is a severse systemic infection with high mortality and is responsive to ribavirin therapy. THE FILOVIRUS FAMILY This family of viruses includes two species that are highly pathogenic for humans, the Marburg and the Ebola hemorrhage fever viruses. These two viruses are indigenous to africa and the philippines and were imported to europe and the united states through infected monkeys. In one importation to europe 25 workers who handled blood and tissues from

infected monkeys acquired the infection 7 died. There were also 6 secondary cases but none of the animal caretakers became infected. In the importation of infected monkeys from the philippines to the united states, many of the imported monkeys died during quarantine. The ebolavirus was detected in many of the dying animals. No human was infected in this importation. It appears that these filoviruses are of importance to workers in facilities that handle imported monkeys. The filoviruses are negative-sense single stranded RNA viruses. These viruses are enveloped and have a unique bacilliform morphology. ARBOVIRUSES Arboviruses is a term frequently used in medical literature. This term is derived from arthropod-borne viruses. Arboviruses include all viruses that are transmitted between vertebrate hosts by the bite of arthropod vectors. To be a successful arbovirus, the virus must have a veremic phase of high intensity in the vertebrated host and the capability of multiplying in the athropod vector, this grouping of viruses by the mode of transmission is an epidemiologic classification. Arboviruses include species in five families of RNA viruses (togavirus,flavivirus, rhabdovirus,reovirus and bunyavirus). The more important arboviruses in the united states cause acute encephalitis in humans. Theses viruses are St. Louis , La Crosse, Western and Eastern equine encephalitis viruses, belong to the togavirus , flavivirus and bunyavirus families and are controlled by mosquito abatement program.

SUMMARY 1. Rhabdoviruses have a unique morphology ( bullet shaped )

2. The rabiesvirus is the only medically important species of rhabdoviruses in the united states. 3. The rabiesvirus is transmitted to humans through the bite of rabid animals. The virus multiplies at the site of inoculation, enters the CNS through the myoneural junction and the motor nerve and induces a rapidly progressing acute encephalitis. The incubation period curiously varies from less than 10 days to over 1 year.
4. Virological diagnosis of rabies is important to determine if the biting animal is

rabid and in the differential diagnosis of rapidly progressing acute encephalitis. To determine if the biting animal is rabid the method of choice is to demonstrate rabies antigens in the brain. In the differential diagnosis of acute encephalitis in humans, the method of choice is the demonstration of rabies antibody in the patient`s serum (providing that the patient had not received rabies immunoprophylaxis).
5. Rabies in the united states is primarily a disease of the wildlife mammals. Skunks,

raccoons, foxes and bats accounted for 87% of reported rabies in animals in 1987; dogs and cats only 7%
6. Prevention of rabies in humans in achieved by mandatory rabies immunization of

dogs and cats, preexposure immunization of persons at high risk of animal bites, and postexposure immunoprophylaxis of persons exposed to rabies. 7. Rabies vaccine for human use contains inactivated rabiesvirus. Postexposure immunoprophylaxis consists of the administration of human rabies Ig and a course of rabies vaccine. 8. The morphology of reoviruses is unique in that the arrangement of capsomeres gives the appearance of a wheel, especially striking for the genus rotavirus 9. The genome of reoviruses is also unique in that it is double-stranded RNA (also segmented) 10. The more medically important reoviruses in the united states are the rotaviruses that cause winter infantile diarrhea. 11. The target of rotaviruses is the intestine epithelium.

12. The feces of infected persons contains rotavirus in high concentration. The virus is

transmitted by the fecal-oral route. Over 90% of preschool children in the united states have rotavirus antibodies. Little is known about immunity to reinfection by the homologous and heterologous types. 13. Rotaviruses are the major but not the sole cause of viral gastroenteritis in the united states.
14. Bunyaviruses of medical importance in the united states are the LaCrosse

encephalitis and the hantaviruses. The former is an arbovirus occuring primarily in the great lakes region. The latter causes a severe infection (hantavirus pulmonary syndrome); the infection is acquired through close contact with infected rodents. 15. Coronaviruses are respiratory pathogens of minor medical importance. 16. Some caliciviruses (norwalk virus ) are capable of causing acute gastroenteritis.
17. The arenavirus of medical importance in the united states is the lymphocytic

choriomeningitis virus. It is capable of causing aseptic meningitis and encephalitis. Humans acquire infections through contact with the urine of infected rodents. 18. The marburg and the ebola hemorrhagic fever viruses (filoviruses) cause severe infections and high mortality in humans. They are indigenous to africa and the philippines and have been imported to europe and the united states via infected monkeys. Handlers of blood and tissues from infected monkeys are at high risk of acquiring the infection. To date, human infection has not been documented in the united states.
19. Arboviruses ( arthropod-borne viruses ) include all viruses that are transmitted

between vertebrates by bites of arhropod vectors. These viruses have a viremic phase in the vertebrate host and also multiply in the arthropod vector. The more important arboviruses in the united states cause acute encephalitis in humans ( St.Loius, Western and Eastern equine and LaCrosse encephalitis viruses) belong to the togavirus, flavivirus, and bunyavirus families and are controlled by mosquito abatement program. REVIEW QUESTIONS

1. Rhabdovirus d) has the morphologic appearance of a bullet 2. Rabiesvirus c) is a rhabdovirus 3. About the pathology is acute encephalitis. a)its principal pathology is acute encephalitis 4. Rabies e) all of the above 5. Effective rabies prevention measures include e) all of the above 6. Virologic confirmation of clinical impression (diagnosis) of rabies a)in animals is generally established by the demonstration of rabies antigens in the brain of the animal. 7. Rotavirus e) all of the above 8. Rotavirus e) all of the above 9. Identify the incorrect statement about arboviruses. d) the most effective method of preventing any arbovirus infection is a mosquito abatement program.
10. Hantavirus

e) respiratory syndrome is characterized by flu-like syndrome followed by rapidly progressing respiratory failure.

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FAKULTAS FARMASI UNIVERSITAS ANDALAS 2011