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.
You mentioned that PVM and RSV are very similar, and I think, just as Ally does, that the environment of the lab probably is conducive to the spread of PVM. I know that RSV, apart from being able to survive without a host for a few hours or more, spreads very easily in close quarters and by physical contact. It also is transmitted by aerosol effectively; this makes me wonder if perhaps the way the lab rats are kept (separate cages vs. mixed in one cage) or the air they breathe aids the spread of PVM. Also, regarding humans as carriers, I think we can certainly help transmit disease even if we don’t get sick from it ourselves, especially if conditions for spreading it to the environment of a lab and then on to rats are right. I believe we discussed a similar example (SV40, if I recall correctly?) in class some weeks ago.
I think that there is pretty significant variation between inbred mouse strains. Furthermore, the article mentions that in studies with PVM-infected wild mice there tends to be a milder infection, which I would imagine is at least part of the reason why it is not transmitted. Along the same lines, I was thinking about our discussion two weeks ago about the possibility of strange mutations when something is maintained in a lab for a long time; I do not know a lot about pet mice but I would imagine they are also often inbred and may mutate as a result, complicating our understanding of the causes of PVM infection.
http://ajplung.physiology.org/content/291/3/L426.full
Is susceptibility dependent on virus strain and if so, can it be increased by local and systemic stressors? PVM appears to be a short lived virus. Is it safe to assume that wild rats may become infected with pneumonia but is less likely due to decreased transmission in a larger environment? The lab setting confines the mice to a small limited area in which they have contact and share the same air and possible the same resources (food and water). Could one hypothesize that pneumonia is present due to the physical constraints we place on the lab mice (confining them in a limited environment) thereby increasing virus replication and transmission within the small population?
Is PVM prevalent in most strains of mice used for laboratory work, or only specific strains? Throughout the papers we’ve been reading, researchers use different strains to contribute to their experiments. For example, we read a paper in which four different strains of mice were used to test immune response against a virus. Each strain displayed a different level of immunological efficiency ranging from immunologically deficient to highly resistant. Does human-mouse interaction only lead to PVM infection in “weaker” mice, or does PVM affect most mice in the same way?