Significance of recently discovered parvoviruses might not be obvious for years – review

The family Parvoviridae contains many of the smallest known viruses, some of which result in fatal or debilitating infections.
The family Parvoviridae contains many of the smallest known viruses, some of which result in fatal or debilitating infections.. Photo by bambe1964

Scientists have sounded a note of caution around the large number of parvoviruses discovered in recent years, saying the significance of any newly discovered virus is not always obvious at first.

The family Parvoviridae contains many of the smallest known viruses, some of which result in fatal or debilitating infections.

In recent years, advances in viral discovery techniques have dramatically increased the identification of novel parvoviruses in both diseased and healthy animals.

While some of these discoveries have solved mysteries around the cause of well-described diseases in animals, many of the newly discovered parvoviruses appear to cause mild or no disease, or disease associations remain to be established.

Mason Jager and his fellow Cornell University researchers, writing in the Virology Journal, set out in their just-published review to discuss parvoviruses that infect vertebrate animals, with a special focus on pathogens of veterinary significance and those discovered within the last four years, including several found in horses.

Sir Arnold Theiler
Sir Arnold Theiler (1867-1936).
National Photo Company, Public domain, via Wikimedia Commons

Recent parvovirus discoveries in horses belong to the genus Copiparvovirus. Viruses in this genus have been identified only in mammals so far, and the clinical significance of most remains in question.

Copiparvoviruses were first identified in domestic cows and pigs using DNA sequencing, then equine parvovirus-hepatitis (EqPV-H) was identified in horses.

Severe hepatic necrosis, or serious liver disease, was first described in horses in 1918 by Sir Arnold Theiler and became known as Theiler’s disease. Thousands of horses were vaccinated for African Horse Sickness by administration of pooled horse serum along with live virus. Four to 24 weeks after treatment, 2 to 18% of the horses succumbed to liver necrosis.

Some unvaccinated horses living with vaccinated horses also developed liver necrosis, while horses on properties without vaccination had less or no hepatitis. These findings suggested the condition to be both transmissible and contagious, although an infectious agent was not identified.

One hundred years later, in 2018, EqPV-H was identified by next-generation sequencing of a liver sample from a horse that died of Theiler’s disease, and was confirmed to be the primary pathogen in Theiler’s disease cases. It appears that EqPV-H mostly causes subclinical or mild hepatitis, with severe liver problems (Theiler’s disease) being a rare outcome.

There is a prolonged period with high levels of the virus in the blood before the onset of hepatitis. It remains to be determined whether pathology is a direct effect of the virus or is immune-mediated.

“EqPV-H is present worldwide and both viral infection and presence of viral DNA are common in horses,” the authors noted, with a serum prevalence based on molecular-based testing of 8–37% and seroprevalence of 15 to 35%.

Analysis of historical samples of horses with Theiler’s disease from 1981 demonstrates that this virus has been circulating for at least 40 years.

Its transmission via administration of equine biologic products is well documented, and other modes of transmission are being explored. A seasonal pattern of Theiler’s disease cases in the summer and fall suggests an insect vector, the authors noted, although a horse fly transmission study did not result in viral spread.

“Oral, nasal, and fecal shedding of viral DNA has been demonstrated and successful oral transmission of one single horse reported, however, the primary route of transmission is not yet known.”

The review team said that while the findings to date provide strong evidence of the virus’s disease-causing abilities, much remains to be determined, including what governs tissue response to the virus and influences disease severity.

Two other copiparvoviruses have also been identified in horses. The first was discovered in 2015 in a cerebrospinal fluid sample from a horse with neurological signs and leukocytic pleocytosis (an abnormal increase in the number of lymphocytes in the cerebrospinal fluid).

This viral DNA, named horse parvovirus-CSF, was also detected in Thoroughbreds in China in 2018 and in molecular-based analysis of samples from horses with unexplained neurological or respiratory signs. In the latter study, another copiparvovirus was identified, tentatively named equine copiparvovirus (EqCoPV).

The review team traversed other parvoviruses that infect a range of animals, including some that are endangered.

Many of these newly discovered viruses are likely part of the complex virome of their host species, and cause little or no disease, they said, while others may be pathogens causing diseases for which a cause has not previously been identified.

Most parvoviruses likely cause little or no disease in immune-competent hosts and the few that are consistently associated with disease appear to be the exception, they said.

The authors noted that the number of parvoviruses and parvoviral sequences has increased dramatically in recent years because of improvements in viral discovery approaches.

“A better understanding of these parvovirus infections, and identification of those with pathogenic potential, will help to explain the etiology (cause) of many diseases, and might increase the chances of rescuing those animal species that are endangered,” they said.

“Lastly, as shown by the recent emergence and widespread impact of SARS-CoV-2 (Covid-19) as well as by the pandemic emergence of canine parvovirus in the 1970s, the significance of any newly discovered virus is not always obvious at first.

“This review clearly shows that we can expect the same for parvoviruses, since new pathogenic viruses continue to be identified around 100 years after the first parvovirus diseases were reported.”

The review team comprised Jager, Joy Tomlinson, Robert Lopez-Astacio, Colin Parrish and Gerlinde Van de Walle.

Jager, M.C., Tomlinson, J.E., Lopez-Astacio, R.A. et al. Small but mighty: old and new parvoviruses of veterinary significance. Virol J 18, 210 (2021).

The review, published under a Creative Commons License, can be read here

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