FCV Adapts, Evolves Into New Strains
One vaccine for all variants probably won’t be possible.
Posted: Sept. 27, 2011, 9:40 p.m., EDT
By Rob Armstrong, DVM
For Feline Practice
When David Bowie sang “Time may change me,” he may have been writing of feline calicivirus (FCV). This virus is not content to live the peaceful life of genetic stability adopted by its feline respiratory disease associate, feline herpesvirus-1 (FHV), but rather is constantly morphing and shifting into new strains. Why does FCV behave this way, what are the implications for cats, and what are the implications for feline vaccines?
A major reason for FCV’s mutability is its simple genetic material, which comprises a single strand of RNA. When the virus infects a cat’s respiratory cell (or perhaps some other location in the body) and wants to replicate, it first has to convert this single strand of RNA back to DNA for duplication, then make multiple copies of the DNA back into RNA again, to be subsequently packaged and sent out as fresh virions looking for new cells.
It is easy to see that this process can open multiple opportunities for changes or mutations to the RNA base order. Additionally, as there is no second strand of genetic material in the virus that might serve as a correction template to match the base pairs, then any change in the genetic material will be quickly represented as an alteration in the virus structure.
In contrast, FHV, with its double strand of DNA, has the stability of a Swiss bank (and perhaps the secrecy, too, as it likes to stay hidden within nervous tissue when not actively out and about causing disease).
Once these new FCV variants are released within the cat, they either have to compete for the ability to infect additional cells within the cat, or they have to shed into the environment in hopes of finding another cat to call home. This competition has led FCV into new tissues, away from the upper respiratory tract favored exclusively by FHV and into the lungs, joints, bladder and other areas.
Apparently, FCV may be shed in the urine and feces along with the more traditional transmission via respiratory secretions.
FCV has an advantage in its efforts to jump from cat to cat because it does not have a limited window and can survive a little longer in the environment—perhaps even for a week or more—compared with the enveloped FHV. FCV also is a little more resistant to the effects of disinfectants.
The competition between FCV strains to infect cells within the cat and the need for FCV strains in the environment to find new cats to infect leads to selection for FCV strains that are best able to infect cat cells. There are now multiple described FCV strains with a varying ability to infect cats and cause disease.
Cats acquiring FCV infections can develop a variety of clinical signs—not just the oral ulceration for which this virus is best known. Some cats may get infected with a non-pathogenic strain and remain apparently healthy; other cats may develop fever and respiratory disease (perhaps including oral ulcers); still other cats may become lame, either with or without respiratory disease.
New Strains Arise
Occasionally, cats may develop very severe signs associated with a viral attack on blood vessels, including edematous feet and facial swelling followed by hemorrhage from bodily orifices and, potentially, death. The FCV strains capable of causing more severe disease have been called “virulent systemic,” or VS strains, although the “systemic” part may also be applied to non-virulent strains. Confirmation of virulent calici strains using virus isolation and PCR testing is important because of the severe and infectious nature of the virus.
|Oral ulcerations are the hallmark of feline calicivirus infection. But cats can develop a variety of clinical signs, including fever, respiratory disease and lameness.Photos Courtesy of Merck Animal Health.|
Many FCV-infected cats become carriers and will shed virus, some possibly even shedding virus for the rest of their lives. It is possible that one in four cats is shedding calicivirus to some extent, and of course the viruses being shed will not all be the same strain because of the virus’s genetic variability. Therefore, it is no surprise that there are many FCV strains or that new and potentially harmful strains will continue to arise.
The infectivity of the virus, the high risk of exposure for susceptible cats and the potential for a variety of potentially serious clinical signs make it important to immunize cats against FCV, and this vaccine is recognized as a core antigen by the American Association of Feline Practitioners. There is also good immunological news for FCV vaccines, because serum antibody titers and local mucosal responses are helpful in protecting against infection.
We know that FCV vaccination can provide protection for longer than one year because in one study kittens were vaccinated with a modified live calicivirus vaccine and three years later were protected against oral ulceration from a challenge with FCV. Standard modified live virus FCV vaccines do a good job in protecting cats against clinical signs of disease following exposure to many common variants of the virus, although vaccinated cats may still become carriers and shed virus.
Currently, no vaccine has been shown to protect against all strains of the virus.
Could a vaccine containing additional FCV strains help to generate wider immune protection? The concept is promising and one vaccine manufacturer has tried this approach. This vaccine proved that it induced a protective immune response in a challenge test against the same isolate used to make the vaccine. However, as with almost every aspect of vaccinology, there are gains and losses to be taken into account and many questions remain.
Each time there has been an outbreak of severe disease associated with FCV it seems that—as you might expect with this virus—a different variant is responsible.
It is just not possible to test a vaccine against every new virulent strain and questions remain as to how wide the strain protection will be. Unfortunately, it is probably not possible to immunize cats against all potential FCV strains with one vaccine.
Additionally, if a strain of FCV is particularly virulent, then a live version of the virus in a vaccine may not be a good idea because of the potential for vaccine-induced disease, and a killed virus vaccine is needed. However, to ensure a sufficient response, the killed virus vaccine will most probably need to include an effective adjuvant despite possible risk of a subsequent local reaction.
Dr. Armstrong is a technical services veterinarian for Merck Animal Health. He earned his DVM degree in 1982 and DVSc in 1989. He is author of several peer-reviewed publications on companion and food animal topics and has spoken at national and international confererences.<Home>
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FCV Adapts, Evolves Into New Strains
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