Contributed by guest blogger: Alix Zongrone ’12

Pneumonia virus of mice, or PVM, is the leading cause of pneumonia in laboratory mice; however, lack of evidence of PVM in wild rodents has left scientists in the dark with regards to the history and natural host of the virus. Because PVM is mostly found in captive settings (i.e. laboratories, pet shops, etc.) and PVM-neutralizing behavior has been observed in human cells, it has been suggested that human contact may play a pivotal role in the virus’s spread. Several studies have sought to investigate the prevalence of PVM in humans and its role in human respiratory infection; however, since PVM is closely related to human respiratory syncytial virus, or RSV, it is difficult to make sound conclusions based on this evidence alone.

Due to the evidence of PVM in humans, researchers inoculated two different non-human primate species with PVM to investigate replication activity of PVM in these mammals. They found that, over the course of twelve days, most of the samples exhibited viral replication as well as viral shedding. Although not all of the animals showed virus replication and shedding behavior, PVM antibodies were found in all test animals, suggesting that infection did take place, but replication was highly restricted. Though PVM was observed to not replicate well in non-human primates, human lung epithelial cells exhibited similar permissiveness of both PVM and RSV in vitro.
Controlling the interferon (IFN) immune response is a known mechanism of successful viral replication in the host. Researchers investigated the ability of PVM to block IFN response to further explore PVM host range restriction. The virus demonstrated an ability to block IFN response in these human epithelial cells thanks to the NS2 protein. However, a Western blot was used to compare proteins made from PVM and RSV and  PVM-neutralizing activity specificity was also determined. Humans were tested for PVM antibodies to examine whether an immune response was triggered. No PVM antibodies were found in the human sera, and no reactivity between PVM proteins and observed PVM-neutralizing behavior was recorded. This demonstrates a lack of immune response in the human cells.
Although PVM was observed to replicate in vitro in human epithelial cells, the results remain inconclusive as to whether or not the virus should be considered a human pathogen. The lack of permissiveness in non-human primates suggests that the virus may not actually cause infection in humans. This is supported by the lack of reaction shown between PVM proteins and PVM-neutralizing activity in the Western Blot.
Questions remain as to the nature of the PVM-neutralizing activity in human serum as well the origin of PVM and its natural host. Is that which is categorized as PVM-neutralizing behavior not actually PVM-specific? What is causing PVM in captive laboratory mice but not in wild rodent species?  Finally, what could possibly be the natural host of pneumonia virus of mice, if not mice?

Link: http://jvi.asm.org/content/86/10/5829.abstract?etoc

Alix Zongrone is a senior at Vassar College, majoring in biology.