Parvovirus (mice – MVM and MVP, rats – KRV/RV, H-1, RPV, and RMV)

Prevalence
  • Mice – subject to two different autonomously replicating types:
    • Minute virus of mice (MVM)
    • Mouse parvovirus (MPV-1, -2 and -3) - predominant
  • Amongst the most prevalent viruses in contemporary laboratory mouse populations – due to persistence in infected animals and the environment
  • Rats – naturally susceptible to 4 serotypes:
    • Kilham’s rat virus (KRV/RV) – most pathogenic
    • Toolan’s H-1 virus (H-1)
    • Rat parvovirus (RPV-1 and -2)
    • Rat Minute Virus (RMV)
  • Subclinical infections common among laboratory rats
 
Significance
  • Immune dysfunction is probable in mice and rats
  • Mice and rat parvovirus are oncolytic and oncotropic – explored as potential anti-cancer agents
  • Rat parvoviruses may affect studies involving fecal development
Disease
  • Single stranded DNA viruses
  • Clinical disease seldom present in immunocompetent mice, but virus has significant immunomodulatory effects and are refractory to effective eradication from contaminated mouse colonies
  • Dependent upon the S phase of the cell cycle for virus replication – induce cytolytic disease only in dividing tissues (including lymphoid tissues undergoing antigenic stimulation)
  • Replication limited to certain cell types that bear the appropriate viral receptors
  • Following oral inoculation, mouse parvovirus initially replicates in intraepithelial lymphocytes, lamina propria, and endothelium of small intestine
  • Disseminate into kidney, intestine, lymphoid tissues, liver, and lung
  • Virus shedding documented in urine, faeces, and oropharynx
  • Natural infection of immunocompetent is clinically silent
  • Experimental infection of neonatal with MVM – mortality due to:
    • hemorrhage, hematopoietic involution, and renal papillary infarction
  • Infection of pregnant animals - increased number of uterine resorption sites in dams, runting, ataxia, cerebellar hyperplasia and jaundice in pups
  • Rat juveniles - dyspnea, ruffled hair coat, muscular weakness, and cyanotic scrotums
  • Rat adults (mostly due to RV infections) - congestion of lymph nodes, loss of body fat, and scrotal hemorrhage, with peri-testicular fibrinous exudation (splenomegaly, icterus, and ascites are variable)
  • Microscopic changes may be present in brain, liver, and testes
Transmission
  • Through faeces and urine by oronasal exposure
  • Contact with infected animals, contaminated fomites, and maternal milk
  • Slow rate of cage-to-cage spread
  • Known contaminant of transplantable tumors and cell lines
  • Transplacental transmission demonstrated in pregnant rats inoculated with high doses – resulting in infertility and fetal resorption
  • Neonatal mice protected from infection by seropositive maternal antibody in enzootically infected colonies
  • Mice resist reinfection with homotypic virus, but are susceptible to heterotypic serotype – high frequency of dual MPV and MVM infections
  • Requirements for dividing cells for replication – results in frequent contamination of tumor cell lines and tumor virus stocks
Diagnosis
  • Preferred – Seroconversion
  • Colony surveillance challenging due to inefficient cage-to-cage transmission
  • There are specific assays for the structural antigens (VP – specific to each Parvovirus) as well as for non-structural antigens (NS- common for all Parvoviridae)
  • ELISAs detect antibody to both MVM and MPV (rNS1 ELISA only used for rats – low sensitivity in mouse serum samples)
  • PCR detection in tissues (MLN optimal) and faeces
  • Serological assays prone to low level false positive if sample preparation is not optimal
  • Differential diagnoses include – bacterial septicemias, chronic wasting due to agents such as Mycoplasma pulmonis, and trauma
  • MAP test and virus isolation, including tissue explant cultures – more labour-intensive methods
Strains
  • Total number unknown - more isolates and stains are likely to be discovered
  • Antigenically distinct, although NS-1 protein highly conserved across all parvoviruses
Duration
  • MVM infection is limited in duration, with recovery (infant and immunocompetent mice)
  • MVP infection is typically persistent (mice of all ages) – juvenile may transmit virus more efficiently (may be present for up to 14 weeks)
  • Persistence of parvovirus infections can occur in rats – depend on continuous availability of susceptible animals to permit propagation
Durability
  • Extremely tough and resistant to heat (80°C 2 hours or 40°C 60 days), drying, pH 2-11, chloroform, ether, alcohol, and lipid solvents
  • Inactivated by formalin, 13-propiolactone and oxidizing agents
Screening
  • All colonies – quarterly
  • Commercial breeding colonies – more frequently as pathogen becomes established in Australia
Prevention and Control
  • Pathogen exclusion by:
    • regular health monitoring of supplier sub-populations, transport in filter boxes, quarantine at receiving institution with serology testing 2 weeks post arrival
  • Post infection:
    • caesarean rederivation, embryo transfer, test and cull
  • Strict husbandry protocols, decontamination procedures and efficient barrier conditions are essential for success
Reading
  • Stephen W. Barthold, Stephen M. Griffey & Dean H. Percy. Pathology of Laboratory Rodents and Rabbits (Fourth Edition), 2016
  • Laboratory Animal Science, 46(4):370 -380