Rhabdoviridae

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Rhabdoviridae

• PROPERTIES
• Bullet shaped, enveloped virion with helical
  nucleocapsid
• Genome is negative sense ss RNA
• Large glycoprotein peplomeres G protein
• Neutralizing antibodies are directed against G
  protein epitopes
• Cytoplasmic replication virions bud from
  cytoplasmic membrane
• Some rhabdoviruses cause RAPID CYTOPATHOLOGY
  e.g. vesicular stomatitis virus, others are
  NONCYTOPATHIC e.g. rabies
• During replication, defective interfering
  particles DI are commonly formed. DI
  particles are deletion mutants with greatly
  truncated genome T particles that interfere
  with replication of normal infectious virions

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Rhabdoviridae

• Rhabdoviruses are thermolabile, sensitive to UV
  light, and are readily inactivated by
  detergent-based disinfectants
• e.g. QUATS Zephiran, Cidex and Nolvasan
• Genera
• Genus Lyssavirus Rabies virus
• Genus Vesiculovirus Vesicular stomatitis virus
• Genus Ephemerovirus Bovine ephemeral fever
  virus
• Genus Novirhabdovirus Infectious hematopoietic
  necrosis virus of fish

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Rhabdoviridae

• Genus Lyssavirus Gr. Frenzy
• Genus contains rabies virus and rabies like
  viruses MOKOLA virus
• Lagos bat virus
• Duvenhage virus
• European bat viruses 1 and 2
• Australian bat lyssavirus
• BATS are the reservoir hosts
• Lyssaviruses are relatively noncytopathogenic,
  thus encephalitis and death occur in many cases
  of infection with little or no cell destruction

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Rhabdoviridae - Rabies

• Rabies latin rage
• One of the oldest and most feared disease of
  humans and animals, most lethal of all infectious
  diseases
• Distribution worldwide
• Rabies free
• Japan, New Zealand, hawaii, Antartica, some of
  Europe, Great Britian, most Caribbean

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Rabies

• Australia Australian bat lyssavirus
• NA and Europe, wildlife threat is increasing
• Worldwide dog rabies is the cause of
  40,000-50,000 human cases/year
• Cattle rabies is a problem in Central and SA

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Rabies

• Hosts all warmblodded animals have variable
  degrees of susceptibility
• Foxes, coyotes, jackals, wolves and certain
  rodents are among the most susceptible animal
  groups
• Skunks, bats, raccoons, rabbits, cattle, some
  members of the Felidae family and Viverridea
  civet, mongoose etc. High susceptibility

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Rabies virus

• Etiologic agent lyssavirus
• In north america six lyssavirus strains have
  been identified
• Two skunk strains, an arctic fox and red fox
  strain, gray fox s train, dog/coyote strain and a
  racoon strain
• Virus extremely labile when exposed to UV light
  and heat
• At 20 degrees C virus cannot survive for more
  than 25 hours in carcasses

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• Transmission bite, scratch of rabid animal with
  the virus in its saliva Aerosol transmission in
  cave dwelling bats Human rabies from corneal
  transplant
• Skunks most important for perpetuation of
  wildlife rabies problem. They account for most
  causes of cattle rabies
• High prevalence
• Excretion of large quantities of virus in their
  saliva during the prolonged period 4-18 days of
  clinical disease

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Rhabdoviridae - Bats

• Bats ability based on protracted clinial course
  not a subclinical carrier state
• Subclinical infection can progress to more
  advanced clinical disease during times of stress.
  
• Survival rate is high in bats
• Cases of rabies in insectivorous vats
• Vampire bats major roel in human and animal
  rabies in Mexico, Central america, South America
• Latin america 250-500,000 cases per
  annumvampire bats
• Australian bat lyssavirus isoltated from fruit
  eating bat in Queensland- two humans died

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Rhabdoviridae

• Pathogenesis
• infection in muscle until adequate amounts reach
  motor or sensory nerve endings in the muscle or
  skin
• Virus shed from myocytes into extracellular
  spaces, bind to Ach receptors other receptors
  facilitating its entry into nerve endings
• 2nd phase of infection begins when the virus
  progresses centripetally to the CNS via the
  axoplasm of the peripheral and central nerves
• The virus reaches the limbic system where it
  replicates extensively, leading to the furious
  form of rabies. Spread within the CNS continues
  with replication in the neocortex, resulting in
  the dumb or paralytic form
• Late in infection, virus moves centrifugally from
  the CNS down the peripheral nerves to a variety
  of organs including the adrenal cortex, pancreas
  and the salivary glands via cranial nerves
• Extensive replication in the salivary glands
  results in HIGH CONCENTRATIONS OF VIRUS IN THE
  SALIVA

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Rhabdoviridae Pathology and Immunology

• Pathology -
• Histopathologic examination of the brain reveals
  that many neurons are infected.
• No frank cytopathology
• little inflammatory cell infiltration
• minimal target damage
• Lethal neurologic dysfunction
• Immunology Humoral and cell-mediated immune
  responses cannot be detected during the time the
  virus moves from the site to the bite to the CNS
• Infection is noncytopathic in muscle and nerve
  cells
• Very little viral antigen is release to stimulate
  host defense mechanisms
• NEURONS DONT EXPRESS MHC CLASS I PROTEINS

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Rabies Clinical Features

• IP 14-90 days, but may be longer
• IP is influenced by dose, strain of virus, degree
  of innervation and site of inocultion
• Ascension in nerves is 8-16 mm per day
• Prodromal period period of virus shedding and
  change in temperament before obvious clinical
  disease is observed
• 2 clinical forms initial furious form and a
  terminal dumb form
• Death results from respiratory failure
• A higher proportion of cats and horses exhibit
  fury than is the case for cattle or other
  ruminants or laboratory animals
• In dogs or cats, rare individuals survive more
  than 10 days after virus is first shed into the
  environment

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Rabies Diagnosis

• Diagnosis
• Direct FAT demonstrate rabies antigen in touch
  impressions of brain tissue (medulla, cerebellum,
  hippocampus)
• Reverse transcription-polymerase chain reaction
  RT-PCR to test for the presence of viral RNA in
  the brain of the suspect animal
• Antemortem diagnosis humans only
• FAT, RT-PCR is performed using a skin biopsy,
  skin bx, corneal impression, saliva

• Negri bodies in the hypothalamus, thalamus, pons,
  cerebral cortex and dorsal horns of the spinal
  cord
• Not all virus positive brains show Negri bodies
  75 in humans, lower in some wildlife species
• Virus isolation by intracerebral inoculation of
  weanling mice with fresh homogenized tissue.
• Control mice are inoculated with extracted tissue
  incubated with specific neutralizing antibody.
• Mice develop encephalitis within 14 days

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Rhabdoviridae- Rabies control

• Rabies free countries quarantine involving
  segregation of dogs and cats in licensed premises
  for 6 months
• Endemic countries Vaccination of dogs and cats
  wildlife vaccination
• Post-exposure treatment in humans
• Wash wound thoroughly with aqueous soap solution
  or QUAT
• Human rabies immune globulin HRIG is used at 20
  IU/kg of body weight half infiltrated around
  the wound, half injected intramuscularly
• US Two human rabies vaccines are licensed
• Human diploid cell-culture vaccine HDCV and
  rhesus kidney cell-culture adjuvanted vaccine
  RVA
• Protocol consists of five 1 mL doses given IM in
  the deltoid area, one each on days 0,3,7,14 and
  28
• If a person was vaccinated previously, NO HRIG IS
  GIVEN, instead, two doses of vaccine are given
  one each on days 0 and 3

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Genus Vesiculovirus Vesicular Stomatitis

• Vesicular stomatitis VS sporadic disease of
  cattle and other ruminants, horses, swine and
  humans
• Characterized by fever and vesicle formation
• Found in the Americas and Caribbean
• Etiologic agent Vesiculovirus 3 serotypes and
  several subtypes exist
• NO CROSS PROTECTION AMONG SEROTYPES
• Indiana serotype, New Jersey serotype, Isfahan
  serotype all 3 subtypes.
• NJ serotype is the most common and has the widest
  distribution
• Virus can remain stable for days or weeks in cool
  water, soil and on vegetation
• It is inactivated in 10 minutes by 1 formalin,
  Roccal (QUAT)etc

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Genus Vesicular Stomatitis

• Transmission contact with contaminated milking
  machines teat and udder lesions
• Ingestion of contaminated fomites mouth lesions
• Arthropods though the virus replicates in black
  flies, sandflies, leaf hoppers, culicoides and
  mosquitoes, mechanical transmission is believed
  to be more significant than biological
  transmission
• Houseflies are mechanical vectors
• Pathogenesis enters the body through breaks in
  the mucosa and skin or by the bites of flying
  arthropods
• Vesicle formation is a result of cell
  destruction, interstitial edema that separates
  the epithelium from underlying tissues
• Spread of lesions occurs by local extension.
  Systemic and viremic phase of infection is
  observed only in pigs and small lab animals

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Vesicular Stomatitis

• Clinical Features
• IP 1-5 days
• Vesicular lesions on the tongue, lips, gums,
  teats and coronary bands
• Oral lesions are accompanied by profuse
  salivation and anorexia
• Uncomplicated cases fully recover in 2 weeks
• Diagnosis
• Virus isolation from vesicular fluids and tissue
  scrapings
• Cell cultures, embryonated eggs and sucking mice
  IC inoculation
• Paired acute and convalescent serum samples
  Antibodies are quantitated using CFT and VN test

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Vesicular Stomatitis - Vaccine

• Prevention and Control
• Vesicular stomatitis is a reportable disease
• Quarantine of affected premises.
• Movement of cattle, swine, and horses from
  affected premises is prohibition until 30 days
  after the last clinical signs or the disease is
  evident with the exception of animals going
  directly to slaughter
• Vaccination USDA approved autogenous killed
  vaccines are available only during outbreaks
  efficacy is in doubt
• Horses no lab tests to differentiate between a
  positive serological reaction due to vaccination
  or natural exposure
• The American Horse Council and AAEP recommend
  that horse owners and vets carefully consider the
  repurcussions from using vaccines some states
  and countries require NEGATIVE BLOOD TESTS FOR
  ENTRY
• Zoonotic Humans flu like symptoms for one
  week

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Genus EphemerovirusBovine Ephemeral Fever 3 d.
sickness

• BEF is a benign
• noncontagious arthropod-transmitted
• Acute febrile disease of cattle and water buffalo
• Distribution Africa, Asia and Australia Never
  reported in N.A.
• Etiologic agent Bovine ephemerovirus 1
  serotype
• Transmission insect vectors have not been
  specifically identified but are believed to be
  Culicoides spp. And possibly mosquitoes

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Bovine ephemeral fever

• Pathogenesis poorly understood
• Virus is associated with the buffy coat fraction
  of the blood
• Site of replication is unknown
• Lesions include a serofibrinous polyserositis
  affecting the joints, pleural and peritoneal
  surfaces. Some lung edema and atelectasis
• Effusion fluids are characterized by the presence
  of large numbers of neuts. The neutrophil
  influx, combined with evidence of increased
  permeability of small serosal vessels, suggests
  that BEF may represent an acute,
  neutrophil-dependent, immune complex
  hypersensitivity
• Clinical Features IP 2-4 days, Morbidity 80,
  Mortality 1-2
• Sudden onset, inappetance, pyrexia, lameness
• Severe drop in milk production in lactating cows
• Excessive salivation, lacrimation, serous nasal
  discharge, drooling, and dyspnea
• Abortion is observed in 5 of pregnant cows
• Recovery is complete in 3 days (2-5), some remain
  recumbent for long periods after the temperature
  returns to normal

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Bovine Ephemeral Fever- Vaccine

• Diagnosis
• Virus isolation is difficult but can be attempted
  by inoculation of infected buffy coat cells into
  cell cultures derived from Aedes albopictus or IC
  inoculation of suckling mice
• FA staining of blood smears prepared during
  viremia
• Paired serum samples ELISA or VN tests
• Control Vector control
• Attenuated vaccines are used in endemic areas
• Recovering animals have long-lasting immunity