(ii) Sendai virus.
Sendai virus (SV) is one of the most important pathogens of mice and rats. Hamsters may also be infected, although their infection is asymptomatic. SV is an ssRNA virus of the family Paramyxoviridae , genus Paramyxovirus , and species parainfluenza 1. Multiple strains have been described. SV is extremely contagious, and transmission is via contact and aerosol infection of the respiratory tract. Natural infection of rats with SV is generally asymptomatic, with only minor effects on reproduction and growth of pups. Natural infections of mice present as enzootic or epizootic infections. Enzootic infections are those endemic to a colony, where the constant supply of susceptible animals maintains the infection. Mice are infected shortly after weaning as maternal antibody levels wane, and they show few clinical signs. Since there is no carrier state, cessation of breeding eventually results in elimination of the infection, although antibody titers remain in previously infected animals. Epizootic infections occur upon first introduction of the virus to a colony. Clinical signs may include teeth chattering, dyspnea, prolonged gestation, poor growth, and death of young mice. Where breeding is occurring, the enzootic pattern eventually takes over.
SV contains HN protein, with hemagglutinating and neuraminidase activities, and F glycoprotein, with cell fusion, cell entry, and hemolytic activities. Conversion of the F glycoprotein to the active form is dependent on host proteases and is inhibited by pulmonary surfactant. However, there are considerable differences in susceptibility to SV among both rat and mouse strains. Among rat strains, LEW and Brown Norway (BN) rats are more susceptible than F344 rats. Among mouse strains, 129/J and DBA strains are among the most susceptible and SJL/J and C57BL/6J are among the most resistant. Because of these strain differences in susceptibility, pathologic lesions vary in severity. The hallmark of SV infection is transient hypertrophy, necrosis, and repair of airway epithelium as the virus descends the respiratory tract. Repair of airway epitheliumresults in epithelial hyperplasia, squamous metaplasia, and syncytial cell formation. Upon reaching the lungs, focal interstitial pneumonia occurs, with inflammatory and hyperplastic changes being most severe around terminal bronchioles, in contrast to infection with Mycoplasma pulmonis , which affects more proximal airways. The lungs appear focally reddened. Viral replication occurs in the respiratory tract for only about 1 week postinfection, so lesions resolve quickly and eventually consist only of loose peribronchiolar and perivascular lymphocyte cuffing. Lesions are more severe and varied when additional pathogens such as M. pulmonis are present. Aged and immunodeficient mice and rats infected with SV develop a severe form of pneumonia, with delayed viral clearance.
There is a considerable volume of literature on immune responses to SV. Immunity to SV is both cell and antibody mediated. Natural infection with SV could profoundly interfere with a wide variety of research efforts involving mice and rats, since SV has been shown to affect rodents in many ways. Reported effects include interference with early embryonic development and fetal growth; alterations of macrophage, natural killer (NK) cell, and T- and B-cell function; cytokine and chemokine production; bronchiolar mast cell populations; pulmonary hypersensitivity; isograft rejection; airway physiology; response to transplantable tumors and lung allografts; neoplastic response to carcinogens; apoptosis rates; and wound healing. Recently, SV has been used experimentally as a gene vector. Natural infection would, of course, interfere with such studies.
