Guest post by Ingrid R. Niesman, MS PhD
Sometimes it’s hard to know which part of me should come out first, the observant and curious scientist, or the deeply passionate cat lover. I registered for the Winn Feline Foundation FIP (Feline Infectious Peritonitis) Symposium based on the opportunity to dive more deeply into the feline medicine scientific world. I never experienced FIP in my cats or had an understanding of feline enteric coronavirus (FECV) or the mutated FIP culprit. I was unprepared to understand the depth of passion surrounding this disease, and the lengths scientists and owners have gone to achieve the breakthroughs in treatment and prevention presented in this two-day symposium.
A brief history of FIP
FIP is a direct predecessor of an original FECV infection. Coronaviruses are, in general, ubiquitous among species, but have a propensity to jump from original to novel hosts, something that is termed a zoonotic exchange.
FIP was not a concern until the middle of the last century, coinciding with the rapid rise of pet ownership worldwide. Whether FECV was endemic in feral populations or originated from a precursor virus in overcrowded antiquated animal shelters or backyard catteries is a question for another day. Today, very few kittens or cats can escape exposure to non-virulent FECV. Most clear the infection easily, but many may still harbor and shed virion particles (the infectious virus) for many months. Transmission is through an oral route. Litter tracking, grooming and even handing by humans spreads this virus throughout a population. The insidious part of an FECV infection rarely occurs, less than 15% of the time. Within this subset, only a small percentage of that group is unlucky enough to develop the full blown pathogenic virulent mutated form, the previously fatal FIP infection.
How FIP develops
FECV is one of the largest single stranded RNA genomes known to date, approximately four times larger than HIV, a similar RNA virus. RNA viruses have rapid mutational changes that can be driven by anti-viral therapies, environmental conditions or any other number of host factors that impact viral propagation. FECV is no exception. During one of the Symposium sessions, Dr. Niels Pedersen, a leading feline virologist at UC-Davis, outlined his lab’s findings on specific mutations in FECV that allow the virus infecting intestinal cells to gaining access to the immune system of host cats.
This is where I sat up and took notice. The virulent infection takes hold in cells that are usually part of the surveillance system – the macrophage. Whereas, FECV barely causes the immune system to yawn, FIPV causes the opposite effect. FIPV infections ramp up the immune system and generate an inflammatory storm of biblical proportions. Inflammation-inducing proteins are regulatory signals that control responses to infections by screaming to hosts that danger lurks and must be dealt with quickly. Levels of these proteins rise rapidly and then quickly decrease as host immune systems take control of the situation. FIPV appears to short-circuit this delicate cycle, leading to full blown FIP.
Understanding clinical pathology from a science perspective: time is of the essence
I learned in the first Roundtable Discussion that perhaps the greatest challenge for clinicians is a lack of tools for a definitive diagnosis. When dealing with a potential FIP case, time is of the essence. Yet, diagnosing an FIP case is involved and based on exclusion of other possible causes. This takes valuable time, additional money and invasive procedures, considerations that are particularly detrimental to the young cats stricken with this disease.
Looking for antibodies to the original FECV virus is one method to demonstrate infection. One protein of FECV can cause a host to produce antibodies. However, these antibodies are likely to cross-react with other coronaviruses, raising the specter of inaccurate results. It was reported in the Discussion Session that antibody detection could be applied to just macrophages instead of whole blood, but reported studies returned high levels of false-positives and require an invasive procedure to obtain the macrophages.
If antibody testing is problematic, is there a molecular approach that could detect the virus? Assays for viral RNA show promise but miss many cases. The current commercially available qPCR test does not appear to detect blood virus levels at all, rendering it useless unless lesions from potentially infected cats are tested. Using tissue markers appears to provide some robust results, but of course this is at the expense of an invasive biopsy of an affected kitty and a lengthy period of time needed to prepare the sample.
What are we missing?
So, where does this leave your local vet? The clinical characteristics, fever, loss of appetite, lethargy, and diarrhea, mimic many typical, treatable conditions. No vet wants to tell an owner that they have either missed the disease or misdiagnosed the condition.
Looking at the fundamental differences between FECV and FIPV may yield a definitive marker, one capable of distinguishing an active case of FIPV. From my scientific perspective, more research into the actual cell biology of FIPV infections could find additional markers useful for clinical assay development. Research equals money, which is lacking for feline medicine discovery. Therefore, the best current recommendation is to use the guidelines laid out by one of many published diagnosis trees to exclude other conditions rather than confirm FIPV. Sadly, this is far from satisfactory when a young kitten’s life hangs in the balance.
From my brief survey of the literature, this is where the field stood a decade ago, stymied by a lack of funding, a dearth of feline specific molecular tools, and a disease that defeats immune regulation. This is the point where my scientific side yields to the empathetic human side.
Part Two: The Cats and Owners Who Fight This Battle
In my next post, I will introduce the reader to the cat and owner side of this disease. These are the frontline soldiers in the battle to contain and ultimately defeat this virus in the face of a true drug war. This heartbreaking war pits scientists and pharmaceutical executives against veterinarians, pet owners, and dying cats.
Ingrid R. Niesman MS PhD is the Director of the SDSU Electron Microscope Imaging Facility at San Diego State University.