Did Kings Kissing Greyhounds Give Us Hepatitis C? Perhaps, but It Doesn’t Mean Service and Therapy Dogs Should Be Kept Out of Hospitals

When the popular media reported that hepatitis C may have originally come from dogs, I got several emails asking if this was going to have an effect on whether therapy dogs should be admitted to hospital settings. I read the scientific paper, and tracked down some related research regarding viruses, and am happy to say that this kind of interspecies transfer should not affect our ability to take dogs into hospitals. Since this is something I do on a regular basis (at Benedictine Hospital in Kingston, NY), I am personally relieved as well.

At least that is the simple answer. The transfer of the virus from dogs to humans, if that is what happened, probably occurred only once, at least 500 years ago, after which the virus that made the transfer, probably itself mutated from the standard virus in dogs, established a foothold and remained a human problem. There are viruses, however, such as a parvovirus that infects both cats and dogs, that can transfer more often between species, and there is no guarantee that this could not happen with other viruses that affect dogs and humans. Nevertheless, such events will remain rare, and the discovery of the strong similarity between human and canine hepatitis C should not alter hospital practices regarding the admission of therapy and service dogs.

Canine and Human Hepatitis. The hepatitis C virus (HCV) was discovered in 1989 (Alter, Choo), and it is now known that 200 million people are chronically infected with this virus, putting them at risk for liver fibrosis, cirrhosis, and hepatocellular carcinoma. Efforts to find homologs of HCV in non-human primates have so far been unsuccessful.

While looking at respiratory viruses of domestic dogs, a team of scientists from American and English universities and research facilities (Kapoor et al.) found a virus genetically similar to HCV, which they have tentatively named canine hepacivirus (CHV). The virus belongs in a group of probably four genera of viruses in a family of viruses called the Flaviviridae. The virus is found in respiratory samples, as well as in livers, of domestic dogs.

The team’s results “indicate that hepaciviruses are not restricted to primates and suggest the possibility that HCV may have been introduced in the human population through contact with canines or other nonprimate species.” As with hepatitis C in humans, an analysis of the chemical structure of CHV predicts that infections from it “may be persistent in its natural hosts.” The disease patterns in humans and dogs are different, however. CHV-infected dogs, for instance, have high levels of CHV in respiratory samples, but HCV-infected humans do not. The researchers note that a “significant difference in life span of humans and canines can also affect the disease pattern caused by genetically related viruses.”

The divergence of the human C virus and the canine virus is about the same as between a virus found in humans (GBV-C) and one found in chimpanzees and New World primates (GBV-A), a virus not known to cause disease in humans but which may affect the immune systems of patients with HIV.

A statistical calculation of the time to most recent ancestor (TMRCA) led the researchers to “estimate that the shared common ancestor between CHV and HCV genotypes probably existed between 500 and 1,000 ybp [years before the present].” Reaching this estimate requires some assumptions, and the researchers caution that there are complexities in determining rates of divergence. If the time frame is correct, the common ancestor could have passed from one species to the other during the Middle Ages, a time when kings were kissing greyhounds and paupers slept in kennels.

The researchers note that other non-human primates should be tested for HCV-like viruses, which has not so far been done “because of a primate focus in screening paradigms.” It is possible, however, that “hepaciviruses are primarily canine viruses and HCV in humans arose zoonotically from contact from dogs or other related members of carnivore mammalian order that harbor these types of viruses.” The researchers note that such a zoonotic origin “would explain its high degree of pathogenicity in humans” and the “apparent absence of HCV homolog in nonhuman primates.”

In the stages described by Wolfe, Dunavan, and Diamond by which a pathogen transforms from exclusively infecting animals into a pathogen exclusively infecting humans, HCV has apparently reached the fifth stage, only transmitting between humans.

Canine Parvovirus. A much more recent species jump involves the parvovirus, which moved from cats to dogs (perhaps from a single cat to a single dog) in the late 1960s or early 1970s. Parrish and Kawaoka note that animal viruses may be generalists, infecting a variety of hosts, or specialists, infecting only one or a few host species. Various changes are required for a virus to become a successful epidemic pathogen in a new host. The transfer to a new host likely starts with only a single virus.

The parvovirus found in cats (FPV) since the early part of the twentieth century has been recognized since the 1940s as a natural pathogen of minks, foxes, and raccoons. Canine parvovirus (CPV) was first observed in May 1978, when two new diseases were reported: (1) myocarditis leading to sudden death in neonatal pups, and (2) entiritis accompanied by diarrhea in dogs older than two months. The diseases spread to wild and domestic dogs throughout the world. It remains an endemic pathogen with dogs everywhere.

The FPV and CPV viruses are more than 99% identical in DNA sequence. Serological studies showed that CPV had a low prevalence in European dogs between 1974 and 1976, but spread worldwide in 1978. CPV-like viruses were all derived from the introduction of a single common ancestor (a single mutant virus) from cats into dogs in the late 1960s or early 1970s. A variation of CPV (CPV-2a) occurred in 1979 and replaced the earlier strain (CPV-2) throughout the world.

Dog Flu. Another crossing of species lines has been the transmission of equine influenza (EIV) to dogs (CIV), first recognized as a pathogen of dogs in 2004 when found in greyhounds in Florida, though serological analysis suggested an initial transfer around 2000. CIV is now common in certain regions of the U.S. A recent study (Hoelzer et al. 2010) found that many mutations occurred in infected dogs, but the researchers also argued that “mutations that facilitate adaptation to a new host species might occur transiently in the donor host … and provide a transient reservoir of pre-adapted mutations.” This flu virus seems to constantly throw off mutations, with the chance that some of them will survive and adapt, even in a new species.

Conclusion. Most viruses that infect wildlife and domestic animals do not infect humans, though sustained contact between species increases the likelihood that a virus will adapt and jump across the species barrier. Research in this area is in its infancy, and a good deal more will be learned in the coming years. Many viruses cause few or no symptoms in long-time hosts, and it is sometimes difficult to say where a virus jumped a species barrier. The more animals that are investigated, however, the more zoonotic researchers will be asked if their findings should limit human-animal contact, such as with patients who have diminished immune responses. This is not an argument, however, for keeping dogs from humans, any more than the parvovirus transfer is an argument for keeping cats from dogs, or the flu transfer from keeping horses from dogs. Of course, a sick dog should not be taken to visit patients in any case.

When I take Chloe to a hospital, it remains true that I am much more likely than she is to bring an infection in with me.

Sources: A. Kapoor, P. Simmonds, G. Gerold, N. Qaisar, K. Jain, J.A. Henriquez, C. Firth, D. Hirschberg, C.M.Rice, S. Shields, and W.I. Lipkin (2011). Characterization of a Canine Homolog of Hepatitis C. Virus. Proceedings of the National Academy of Sciences. Approved April 28, 2011. H.J. Alter (1989.) Discovery of the non-A, non-B hepatitis virus: The end of the beginning or the beginning of the end. Transfusion Medicine Reviews, 3, 77–81; Q.L. Choo, G. Kuo, A.J. Weiner, L.R. Overby, D.W. Bradley, and M. Houghton (1989). Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science, 244, 359–362; C.R. Parrish and Y. Kawaoka (2005). The Origins of New Pandemic Viruses: The Acquisition of New Host Ranges by Canine Parvovirus and Influenza A Viruses. Annual Review of Microbiology, 59, 553-586; C.R. Parrish, C.F. Aquadro, M.L. Strassheim, J.F. Evermann, J.-Y. Sgro, and H.O. Mohammed (1991) Rapid Antigenic-Type Replacement and DNA Sequence Evolution of Canine Parvovirus, Journal of Virology, 65(12), 6544-6552 (description of mutation in CPV becoming prevalent after 1986); S.-F. Chang, J.-Y. Sgro, and C.R. Parrish (1992). Multiple Amino Acids in the Capsid Structure of Canine Parvovirus Coordinately Determine the Canine Host Range and Specific Antigenic and Hemagglutination Properties. Journal of Virology, 66(12), 6858-6867; C.R. Parrish, E.C. Holmes, D.M. Morens, E.-C. Park, D.S. Burke, C.H. Calisher, C.A. Lauglin, L.J. Saif, and LP. Daszak. Cross-Species Virus Transmission and the Emergence of New Epidemic Diseases. Microbiology and Molecular Biology Reviews, 72(3), 457-470; K. Hoelzer, P.R. Murcia, G.J. Baillie, J.L.N. Wood, S.M. Metzger, M. Osterrieder, E.J. Dobovi, E.C. Holmes, and C.R. Parrish (2010). Intrahost Evolutionary Dynamics of Canine Influenza Virus in Naïve and Partially Immune Dogs. Journal of Virology, 84(10), 5329-5335; N.D. Wolfe, C.P. Dunavan, and J. Diamond, Origins of Major Human Infectious Diseases. Nature, 447, 29-93.

Thanks to Richard Hawkins and Joann Lindenmayer for bringing additional sources to my attention. My apologies to them and other scientists if I have failed to detect some of the more subtle nuances of the papers referred to. Although at Berkeley in the 1960s I took Chem 8 from Melvin Calvin and attended Gunther Stent's Friday afternoon mol bi seminars, some of the organic chemistry was a bit beyond my reach, and still is.