calici

• Caliciviridae

  • Pathogenic caliciviruses typically cause enteric, oral cavity and upper respiratory, or systemic disease in their respective hosts
  • Latin Calyx meaning "cup" or "chalice"
  • composed of 180 capsid proteins
  • nonenveloped
  • icosahedral shaped virus
  • positive-sense, single-stranded RNA
  • cytoplasmic replication
• Genera in the family Caliciviridae(5)

  • Vesivirus
  • Lagovirus
  • Norovirus
  • Sapovirus
  • Nebovirus
• Norovirus


  Noroviruses cause enteric infections in a wide variety of animal species and are important causes of gastroenteritis in humans
• Murine Norovirus


  • Isolated from immunocompromised mice
  • Initially detected because of sporadic deaths in a colony of mice deficient in the STAT1 and RAG2 genes
  • Immune-deficient mice and wild-type mice are susceptible to oral infection
  • Widely used model for studying human norovirus infection due to their similarities in disease course and pathogenesis
• Distribution of Murine Norovirus


  • MNV has been detected in various regions globally where mice populations are prevalent
  • Commonly found in facilities housing mice used for experimental purposes, especially in academic and pharmaceutical research environments
• Clinical signs of Murine Norovirus


  • MNV typically causes no outward signs of illness in healthy adult mice
  • Immunocompromised mice can experience severe weight loss, diarrhea, and even death
• Transmission of Murine Norovirus


  Transmitted among mice through fecal-oral routes and contaminated environment
• Pathogenesis of Murine Norovirus

  1. Viral attachment and entry

  2. Viral replication

  3. Viral release and cell death

  4. Immune response
• Pathology of Murine Norovirus


  • Disease in select types of immunodeficient mice includes encephalitis, cerebral vasculitis, meningitis, hepatitis, and pneumonia
  • Infection of immunocompetent mice is clinically silent
• Lesions of Murine Norovirus


  • Most commonly affected organ in immunodeficient mice is the liver, where lesions can include inflammation and cell death (necrosis)
  • Other organs that may be affected include the lungs, intestines, lymph nodes, brain, and spleen
• Diagnosis of Murine Norovirus

  • Polymerase Chain Reaction (PCR)
  • Serology
• Treatment and control of Murine Norovirus


  • No specific treatment
  • Most effective way to control MNV is to prevent infection in the first place, this can be done by practicing good hygiene, such as washing hands thoroughly with soap and water after handling mice or their bedding, and disinfecting cages and equipment regularly
• Rabbit Hemorrhagic Disease (RHD)

  • Etiology: Rabbit Hemorrhagic Disease Virus (RHDV)
  • Differential Diagnosis: European Brown Hare Syndrome (EBHS)
• Rabbit Hemorrhagic Disease killed nearly half a million rabbits within six months in China, and spread throughout China, Europe, North Africa, and the Americas, with human intervention sometimes facilitating its spread
• European Brown Hare Syndrome (EBHS)

  A disease primarily affecting brown hares, caused by a lagovirus related to RHDV, but with different host ranges
• RHD is believed to have emerged from avirulent endemic viruses circulating subclinically among wild European rabbit populations
• Mortality rates from RHD exceed 80% with certain virus strains
• RHD is only fatal to rabbits over 2 months of age
• Distribution of RHD


  • After an outbreak in China in 1984 it spread widely
  • Classical RHDV and RHDVa have become endemic in European rabbit habitats
  • RHDV2 was first detected in the United States in 2018 and reintroduced in 2020, spreading across multiple states including Arizona, California, Colorado, Nevada, New Mexico, and Texas
• Reservoir for RHD


  • Domestic and Feral Rabbits
  • Infected rabbit meat, feces, urine
• Transmission of RHD


  • Direct contact (mainly oral-fecal)
  • Fomites
  • Vectors
  • Exposure to infected carcass
• Pathogenesis and Pathology of RHD

  • Linked to intravascular coagulation, likely triggered by liver necrosis
  • Young rabbits are resistant to the disease, possibly due to differences in innate immune response, virus attachment receptor expression, and hepatocyte susceptibility
  • Recent studies suggest strain variation among viruses can influence disease course through immune evasion and the utilization of different cellular receptors
• Lesions in RHD


  • Nasal hemorrhage
  • Pulmonary congestion, edema, and hemorrhage
  • Hemorrhages on the serosal surfaces of abdominal viscera
  • Marked splenomegaly in some animals
  • Zonal (periportal to mid-zonal) necrosis of the liver that imparts an enhanced lobular pattern throughout the organ
• Disease patterns in RHD

  • Peracute infection: sudden death with no clinical signs
  • Acute: may appear quiet, have fever, and an increased respiratory rate for up to 24hrs before death
  • Subacute: jaundice and death of several days up to 2 weeks
  • Subclinical: may occur in some rabbits, characterized by severe jaundice, weight loss, and lethargy. Kits less than 4 to 8 weeks old are infected and shed virus but do not develop clinical signs other than fever
• Clinical signs of RHD

  • Fever
  • Anorexia
  • Apathy
  • Increase respiratory rate
  • Disseminated hemorrhage in all body tissues
  • Rapid death
  • Affected rabbits may have serosanguineous or bloody nasal discharge and exhibit nervous signs
• Laboratory Diagnosis of RHD

  • Immunofluorescence and ELISA tests
  • RT-PCR for rapid infection diagnosis
  • Liver is used for viral detection
  • Reportable disease in the U.S.
• Treatment and Control of RHD

  • Treatment options available
  • Control in commercial husbandry units by preventing virus entry through fomites, infected wild rabbits, or insects
  • Strict quarantine, if ever an outbreak occur
  • Disinfection
  • Vaccines
• RHD is not zoonotic
• European Brown Hare Syndrome (EBHS)

  • Etiology: European Brown Hare Syndrome Virus (EBHSV)
  • Differential Diagnosis: Rabbit haemorrhagic disease (RHD), Acute bacterial infections/septicaemia (Pasteurellosis, Tularemia, Pseudotuberculosis, Listeriosis)
• Hosts for EBHS


  • European brown hares (Lepus europaeus)
  • Northern hares (Lepus timidus)
  • Eastern cottontail rabbits (Sylvilagus floridanus) may be a spillover/dead end host
• Transmission of EBHS


  • Faecal-oral routes
  • Inhalation of aerosols or respiratory droplets
  • Direct hare-to-hare transmission
• Sources of EBHS


  • Other infected hares
  • Fomites, including arthropods as mechanical vectors
  • Aerosols
  • Faeces from infected hare
• EBHS virus, limited to northern and European brown hares, has been detected in Argentina's Buenos Aires province, likely due to European brown hare importation and 1888 release
• Clinical signs of EBHS

  • Sudden death
  • Anorexia
  • Depressed
  • Abnormal behavior
• Laboratory diagnosis of EBHS

  • Immunohistochemistry (IHC)
  • Haemagglutination assays (HA)
  • Multiple enzyme-linked immunosorbent assays (ELISAs)
  • Electron microscopy
  • Reverse transcriptase polymerase chain reaction (RT-PCR)
  • Agglutination of human type "A" or "O" red blood cells at pH 6.4 and at 4°C
• Prevention and Control of EBHS

  • Biosecurity measures
  • Quarantine and serologically tested before introducing
  • No vaccines available
• Transmission routes for European Brown Hare Syndrome

  • Fecal-oral
  • Inhalation of aerosols or respiratory droplets
  • Direct hare-to-hare transmission
• Sources of European Brown Hare Syndrome

  • Other infected hares
  • Fomites, including arthropods as mechanical vectors
  • Aerosols
  • Faeces from infected hare
• European Brown Hare Syndrome (EBHS)

  Viral disease limited to northern and European brown hares, has been detected in Argentina's Buenos Aires province, likely due to European brown hare importation and 1888 release
• Clinical signs of EBHS

  • Sudden death
  • Anorexia
  • Depressed
  • Abnormal behavior