Relevance of novel small animal viruses in UK veterinary practice

In an age of powerful sequencing techniques, it seems new viruses are being discovered every day and the world of known viruses, or “virosphere”, is expanding at an impressive rate.

A number of these viruses have been identified in canine and feline populations – often in a serendipitous manner. But are they able to cause disease in our patients? Could they explain the high prevalence of certain diseases that have no known aetiology?

This article will examine five recently identified viruses of dogs and cats that have raised considerable interest in the world of companion animal infectious diseases.

Feline morbillivirus – a cause of kidney disease?

Feline morbillivirus (FeMV) was first discovered in 2011 as a suspected cause of renal disease in cats in Hong Kong¹. Urine, faecal and blood samples collected from stray cats were screened for novel viruses and, unexpectedly, an unknown paramyxovirus was found in 11.6% of cat urine samples.

The paramyxovirus most closely related to FeMV in companion animals is a canine morbillivirus, better known as canine distemper virus. Researchers had reasoned that if dogs could be infected by such a successful paramyxovirus then perhaps cats had one, too; they were proven correct.

The identification of FeMV in urine led to the hypothesis the virus could be infecting the urinary tract.

Postmortem of two FeMV-infected cats found virus in the renal tubules, as well as evidence of tubulointerstitial nephritis (TIN). An extended study of 27 cats found TIN in 58% of FeMV-positive cats, but only 13% of FeMV-negative cats.

The seminal study from Hong Kong revealed almost 30% of cats tested had antibodies against FeMV. This indicates the virus is relatively common in this region. The first report of a FeMV-positive cat in Europe occurred in a single animal with severe renal disease in Italy². Further cases have also been reported from both North America and South America^3,4, but all cats were clinically healthy. In one case, the virus was shed for at least 15 months with no apparent clinical disease.

In summary, insufficient evidence exists to conclude FeMV is a common cause of renal disease in cats at present. However, more definitive answers are on the horizon as experimental infections have recently been approved. It is anticipated our understanding of FeMV is set to dramatically increase over the next few years.

Canine circovirus – gastroenteritis and haemorrhage?

Canine circovirus was first reported in 2012, following screening of canine serum samples for new pathogens⁵. Circoviruses are tiny DNA viruses with an unusual circular genome. The only other circoviruses known to infect mammals are the porcine circoviruses (PCVs). PCV2 causes a systemic disease of pigs called post-weaning multisystemic wasting syndrome, which is of major economic importance in the swine industry.

Does canine circovirus cause disease? The virus has been identified in the liver of a dog with severe haemorrhagic gastroenteritis and vasculitis⁶. This was initially a chance finding, and the authors then examined tissue samples from 14 other dogs that had died with similar clinical signs.

Canine circovirus was identified in 3 of these dogs, and a conference abstract has now extended this figure to a total of 12 dogs.

Canine circovirus has also been found in dogs with uncomplicated gastroenteritis in several countries, suggesting the virus is an intestinal pathogen. However, canine circovirus has also been found in faecal samples from healthy dogs, and whereas in two studies the virus was found at greater frequency in diarrhoeic dogs^7,8, in a further three studies no significant difference existed between detection in healthy and diseased dogs^6,9,10.

The most recent study published about canine circovirus looked at dogs co-infected with circovirus and canine parvovirus. It was found dogs infected with both viruses had a higher mortality rate than dogs infected with parvovirus alone⁹. However, in summary, no studies to date have been able to conclusively demonstrate the pathogenic effects of this virus. This means the importance of canine circovirus as a pathogen of dogs is still uncertain.

Canine influenza virus – UK respiratory disease?

Various sporadic reports exist of dogs contracting influenza from humans and occasionally horses for many years, but typically these cases have been isolated incidents with no reported dog-to-dog transmission.

This all changed in 2004 when the first canine-specific influenza strain was detected in the US¹¹. Groups of racing greyhounds from tracks across the country started showing signs of severe respiratory disease with up to 10% mortality rates. Genetic characterisation of the influenza virus isolated from these dogs showed the virus originated from an H3N8 strain of equine influenza. Evolution of the equine strain in dogs then resulted in a virus that could transmit directly between dogs, resulting in rapid spread of the virus within canine populations.

By coincidence, at around the same time as the H3N8 canine influenza appeared in the US, a second unrelated canine-specific influenza strain emerged in Asia. However, this canine strain did not have an equine origin, instead evolving from an avian-like H3N2 influenza strain¹². For more than a decade, this H3N2 canine strain circulated only in Asia, but in 2015, it suddenly appeared in Chicago, US. Cases of canine respiratory disease were reported from all over the US within months. To add to veterinary concern, the H3N2 strain can also infect cats, with the first feline cases identified at an animal shelter in the Midwest in 2016.

Fortunately, neither the H3N8 nor H3N2 canine influenza strains have been identified in the UK so far, despite extensive surveillance and many labs offering influenza testing as part of their standard diagnostics panel for canine respiratory disease. This means canine influenza need not be on the differential diagnosis list for respiratory disease here quite yet. In fact, the last reported case of H3N8 in the US was more than a year ago, suggesting this strain of influenza might have actually gone extinct. Canine influenza requires large populations of dogs in close contact – for example, shelters to keep circulating, so if adequate infection control is practised then this virus should be containable.

Felis catus gammaherpesvirus – cause of lymphoma?

The first virus shown to cause cancer in humans was the gammaherpesvirus Epstein-Barr virus (EBV). EBV is better known as the cause of glandular fever, but was proposed more than 50 years ago to be the cause of Burkitt’s lymphoma in a certain proportion of infected humans. Identification of a new gammaherpesvirus in cats¹³ has, therefore, raised significant interest in the oncology community; could this herpesvirus be responsible for causing feline lymphoma alongside the well-studied feline retroviruses?

Feline catus gammaherpesvirus (FcaHV1) is distinct from the most common and well-known herpesvirus of cats, feline herpesvirus-1 (FHV1). Whereas FHV1 typically infects epithelial cells of the respiratory tract and is classified as an alphaherpesvirus, FcaHV1 infects lymphocytes.

FcaHV1 has been identified in 16% of cats in the US¹³ and at a similar prevalence in Asia, Australia and Europe. Up to 32% of cats are seropositive¹⁴ and, as all herpesviruses establish latency, this indicates one in three cats are infected, but may not be shedding the virus at time of sampling. Entire male, adult cats are at increased risk of being infected with FcaHV1 and co-infection of FcaHV1 with FIV or feline haemoplasma species is very common^15,16. This suggests aggressive-male contact is a likely route of transmission.

No studies have yet been published that examine the association between FcaHV1 and lymphoma in cats, so at present no evidence suggests FcaHV1 is a putative cause. But what about canine lymphoma? Despite extensive searching, no comparable canine gammaherpesvirus has been identified. Although 44% of dogs with lymphoma were found to have EBV antibodies in their serum, no herpesvirus DNA was detected in any cancerous cells¹⁷. It will be interesting to see if future research uncovers any new evidence linking canine and feline herpesviruses with cancer, but, at the moment, no proof exists that this is the case.

Canine astrovirus – acute gastroenteritis?

Astroviridae are a relatively obscure family of viruses, so named because of their star-like shape. Astroviruses were first identified in human diarrhoea samples in 1975 and are now estimated to cause up to 10% of childhood gastroenteritis globally. The first canine astrovirus (CaAstV) was reported in 1980, but it wasn’t until 2009 that the first detailed description of CaAstV infection in dogs was published¹⁸.

Since 2009, CaAstV has been identified by PCR across mainland Europe, Asia, South America and the UK. This demonstrates global distribution of this virus, with prevalence rates in dogs reported to be between 2% and 27%^19,20. However, the pathology caused by CaAstV infection in dogs is uncertain. In the UK study, 6% of dogs (4 out of 67) with severe diarrhoea were positive for CaAstV, whereas all of the 181 non-diarrhoeic control dogs were virus-negative²¹.

This raises the possibility of a cause and effect between virus infection and gastroenteritis, supported by several other epidemiological surveys. However, some studies exist, of course, whose results refute a link between astrovirus and gastroenteritis, and to complicate the issue further, co-infections of astrovirus with other gastroenteric pathogens seem to be common.

At present, no commercial tests are available for CaAstV, therefore surveillance is limited to research institutes only. However, given the absence of any virus-specific therapies for canine gastroenteritis, this should not be a concern for case management. Vets need to simply be aware CaAstV is circulating in the UK and, therefore, isolate any suspect infectious gastroenteritis cases, regardless of the results of standard virus screening.

Conclusion

The ability of scientists to detect new viruses in companion animals is still far ahead of our ability to determine how relevant many of these viruses are clinically. Despite numerous studies across the globe that have identified new viruses such as FeMV and canine circovirus, evidence for the ability of these viruses to cause disease is lacking.

The notable exception discussed in this article is canine influenza; the emerging strains of this virus are clearly pathogenic. Thankfully, canine influenza has yet to reach the UK, but continued vigilance for this virus and untold others will be essential.