Pneumonia virus of mice (PVM)

Pneumonia virus of mice (PVM) is a member of the pneumovirus genus, which also contains human and bovine RS viruses, and was originally isolated from apparently healthy laboratory mice. Passage of lung tissue from these mice into healthy recipients resulted in a fatal pneumonia (Horsfall and Hahn, 1939;1940). Subsequently it was shown that the same or a similar virus infected many rodent species (Eaton and Van Herick, 1944; Horsfall and Curren, 1946). PVM is a common infection in laboratory mice in which it is present as either a latent or inapparent injection (Chambers et al., 1980; Parker et al., 1966). Original assignment of PVM to the pneumovirus genus was based on electron microscopic analysis of the virus particle which showed it to be similar to RS virus (Compans et al.,1967). More recent analyses of antibodies from RS virus-infected patients further emphasized this relationship, showing cross-reactivity between the putative nucleocapsid protein of PVM and that of RS virus, though no cross neutralization of infectivity between the viruses has been observed (Gimenez et al., 1984). Similarly a monoclonal antibody generated against PVM cross-reacts with the RS virus phosphoprotein (Ling. and Pringle, 1989).

It has been shown that another paramyxovirus, antigenically related to pneumonia virus of mice (PVM) infects man (Pringle and Eglin, 1986). The data showed that antibodies which effectively neutralized the infectivity of PVM were present in approximately 80% of the adult populations of both the U.K. and Nigeria . The age distribution of seroconversion for this virus was similar to that observed for RS virus. In addition seroconversion was observed in 4 cases, though no symptoms were described. It is not known whether this virus represents a significant proportion of the 25% of unidentified agents causing respiratory disease in children.

We have isolated and characterised cDNA clones representing nine distinct genes of PVM. The sizes of the PVM mRNAs and the derived genetic map were found to be very similar to those of human RS virus. Assignment of polypeptides to six of the nine PVM genes and comparison of these with the corresponding RS virus gene products further emphasised the similarity between these two viruses (Chambers et al., 1990). The nucleotide sequence of all nine PVM genes has been determined and comparison of these with the equivalent genes of RS virus has revealed various degrees of conservation at the nucleotide and amino acid levels. The nucleocapsid, phosphoprotein, matrix and M2 (22K) internal structural proteins of the virus particle are generally homologous to the equivalent RS virus proteins. The nucleocapsid protein is the most highly conserved of all, with 62% homology at the nucleotide level and 60% identity of amino acids. The F glycoprotein of PVM shows homology to that of RS virus, but the F2 portion of the PVM F protein is similar in size to those of paramyxoviruses such as SV5 or Newcastle Disease virus rather than that of RS virus. The G and SH glycoproteins of PVM appear similar in overall structural features such as hydrophobic profile, and potential sites for N-linked glycosylation, but not in sequence, to those of RS virus. The sequences of the PVM non-structural proteins show little or no homology with those of the analogous RS virus NS1 and NS2 proteins. No functions have been assigned to these polypeptides and the significance of the differences between PVM and RS virus are unclear.

These data, reflecting the similarities and differences between RS virus and PVM, together with the information concerning the natural history of infection of both mice and man with PVM or a PVM-related virus indicate that further analysis of PVM is important for several reasons:

The serological relationships between PVM and RS virus described above indicate that the two proteins involved, the nucleoprotein and phosphoprotein have conserved epitopes in both mouse and man. This suggests that the immune response to these viruses may be similar in their respective natural hosts. Important in this regard is the observation that PVM can produce inapparent or latent infections in mice (Horsfall and Hahn,1940; Chambers et al., 1980; Parker et al., 1966). Similarly, the virus is also able to establish persistent infections in athymic mice (Carthew and Sparrow, 1980). This suggests that PVM may be able to reside in an immunologically privileged, or unseen, location in the mouse, or perhaps by altering the quantity or quality of its genetic repertoire can evade immunological surveillance. The precise nature of this virus-host interaction is unknown and requires investigation particularly with regard to its relevance to infection and subsequent re-infection with RS virus in man.
Analysis of PVM allows the use of the extremely well-established mouse model system which is the natural host for the virus. Studies of pathogenicity in this system will give much meaningful information about the important parameters involved in the production of respiratory disease by pneumonoviruses.
PVM is a very common infection in laboratory mice in which it is often inapparent (Chambers et al., 1980; Parker et al., 1966). Since mice are commonly used as model systems for many immunological and other studies of the pathogenesis of infectious agents, the potential effects of a PVM infection must be considered. This is particularly important in considering studies of RS virus pathogenesis in mice where the interpretation of the results may be compromised by the presence of an infection with the related PVM.

References cited

Carthew, P. and Sparrow, S. (1980). Brit. J. Exp. Pathol. 61, 172-175.
Chambers, P. et al (1980). Lab. Animals 14, 309-311.
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Compans, R. W. et al (1967). J. Exp. Med. 126, 267-276.
Eaton, M. D. and Van Herick, W. (1944). Proc. Soc. Exp. Biol. Med. 57, 89-92.
Gimenez, H. B. et al (1984). J. Gen. Virol. 65, 963-971.
Horsfall, F. L. and Curren, E. C. (1946). J. Exp. Med. 83, 43-64.
Horsfall, F. L. and Hahn, R. G. (1939). Proc. Soc. Exp. Biol. Med. 40, 684-686.
Horsfall, F. L. and Hahn, R. G. (1940). J. Exp. Med. 71, 391-408.
Horsfall, F. L. et al (1943). Science 97, 289-291.
Ling, R. and Pringle, C. R. (1989). J. Gen. Virol. 70, 1427-1440.
Parker, J. et al (1966). Natl. Cancer Inst. Mon. 20, 25-37.
Pringle, C. R. and Eglin, R. P. (1986). J. Gen. Virol. 67, 975-982.

This page by: Andrew Easton.