Hantavirus Infection

Hantaviruses are significant zoonotic pathogens of lab­oratory rodents with potentially serious consequences for humans. Rats are susceptible to infection with han­taviruses, and thereby pose a zoonotic hazard to human contacts.

New World that are associated with hantavirus pulmo­nary syndrome (HPS) in humans. It is now apparent that hantaviruses originally evolved in the Old World; they then spread through rodents to the New World across the Bering land bridge. Humans are incidental hosts.

Hantaviruses have caused several laboratory rat-asso­ciated outbreaks of HFRS in Asia and Europe, and these have been traced to infected rats from breeders, wild rodents, and experimentally infected rodents, as well as immunocytomas grown in laboratory rats. The ubiquity of these viruses in wild rodents of North America, includ­ing R. norvegicus, dictates constant awareness of the hazard.

Epizootiology and Pathogenesis

Rats (R. norvegicus and Rattus rattus), several Peromyscus spp., and other rodents and insectivores are natural hosts for a variety of hantaviruses. In the rat, Hantaan virus and Seoul virus (members of the HFRS group) produce no clinical evidence of disease. In experimen­tally inoculated animals, viremia and virus shedding may occur in the saliva and urine, and intracage trans­mission may occur up to 2 months postinoculation. Bite wounds have also been proposed as a major means of intraspecies transmission.

Diagnosis

Serologic assays are available and should be used as part of routine safety precautions in laboratory animal pro­grams using wild rodents or laboratory rats. Because of the high degree of genetic diversity among hantavirus isolates, PCR is not a practical approach to diagnosis.

Paramyxovirus Infections

Members of the family Paramyxoviridae, which infect rats, include members of the subfamily Paramyxoviri- nae: murine parainfluenza virus-1 (Sendai virus) and human parainfluenza virus-3 (PIV-3); and 1 member of the subfamily Pneumovirinae: PVM.

Sendai virus and PIV-3 are antigenically cross­reactive.

Sendai Virus Infection

Sendai virus (murine parainfluenza virus-1) is recognized to cause respiratory diseases in the laboratory mouse, rat, and hamster, and seroconversion also occurs in guinea pigs. Decades ago, Sendai virus was a common and significant pathogen in laboratory animal facilities. Although Sendai virus appears to have disappeared, it continues to be on the exclusion list for serologic sur­veillance for laboratory rodent colonies. Sendai virus in the laboratory rat is recognized to have an additive effect on respiratory infections with M.

Epizootiology and Pathogenesis

Although clinical disease and lesions of the respiratory tract are rarely attributed to Sendai virus infection in the rat, serological surveys from the past indicate that the virus was once relatively widespread in colonies of rats. Trans­mission occurs by direct contact or by aerosols. Following exposure, the virus replicates in the upper respiratory tract, and then extends down the trachea and smaller airways in a stepwise manner. Viral antigen is detectable from approximately 1-7 days. Virus has been recovered from the lung for up to 7 days postinoculation and for up to 12 days when inoculated in young rats. Serum antibody levels may be present for 7 or more months, dropping to low or undetectable levels by 9 months. The pathogenesis of Sendai virus infection in the rat is analogous to Sendai in genetically resistant strains of mice.

Pathology

In rats, necropsied during the acute stages of the disease, there is rhinitis, with focal to diffuse necrosis of respira­tory epithelial cells. Leukocytic infiltrates consist of neu­trophils, lymphocytes, and plasma cells. Residual lesions may persist in the nasal mucosa for 3 or more weeks. In the lower respiratory tract, there is a multifocal hyperplastic to suppurative bronchitis and bronchiolitis, and frequently, focal alveolitis. Alveolar septa are hypercellular, and infil­trating cells consist of alveolar macrophages, neutrophils, and lymphocytes. In the subacute and resolving stages, there is prominent perivascular and peribronchial cuffing with lymphocytes and plasma cells.

Diagnosis

Rats are usually subclinically infected, thus the detection of pulmonary lesions on microscopic examination is frequently the first indication of a possible infectious disease. Acute bronchitis and bronchiolitis, when pres­ent, are diagnostic features of the disease. Other changes are not specific for Sendai virus, and confirmation requires demonstration of a rise in antibody. In sus­pected epizootics of Sendai virus infection, differential diagnoses must include PVM, PIV-3, and rat coronavirus infections. Seroconversion to Sendai virus antigen may occur with natural PIV-3 infection in rats due to cross­reactive antigens.

Parainfluenza Virus 3 Infection

Seroconversion to Sendai virus antigen was detected in rats in a pathogen-free laboratory rat colony without clinical signs, prompting further investigation. Using virus-specific hemagglutination inhibition serology, the agent was identified as PIV-3, possibly of human origin. The virus was isolated and sequenced, confirming it to be PIV-3 with >93% similarity to human PIV-3 isolates. Intranasal inoculation of rats resulted in tran­sient respiratory epithelial necrosis and peribronchiolar mononuclear infiltrations. This event underscored the importance of differentiating natural infections of labo­ratory rats with PIV-3 from Sendai virus.

Pneumonia Virus of Mice Infection

Pneumonia virus of mice, despite its species-centric name, naturally infects mice, rats, hamsters, and possi­bly guinea pigs and gerbils. Infection is usually detected by seroconversion. Intranasal inoculation of F344 rats with PVM resulted in development of gross and micro­scopic lesions by 6 days postinoculation, without clini­cal evidence of disease. Histopathology includes multifocal, nonsuppurative perivasculitis and interstitial pneumonitis with hyperplasia of bronchus-associated lymphoid tissue. These lesions tend to persist for several weeks in the rat. The presence of interstitial pneumonia and perivasculitis attributed to PVM requires confirma­tion by seroconversion. Differential diagnoses include interstitial pneumonia due to Sendai virus, PIV-3, rat coronavirus, and Pneumocystis spp. PVM may be a copathogen in other respiratory diseases, such as myco­plasmal infections. The possibility of interspecies trans­mission to other laboratory animals, such as mice, hamsters, and gerbils, is another consideration.