Contemporary human viruses most likely originated by cross-species transmission from non-human animals. Examples include HIV-1, which crossed from chimpanzees to humans, and SARS coronavirus, which originated in bats. Since the 1989 discovery of hepatitis C virus (classified as a hepacivirus in the family Flaviviridae) the origin of the virus been obscure. During the characterization of respiratory infections of domestic dogs, a virus was discovered that is the most genetically similar animal virus homolog of HCV.
HCV is a substantial human pathogen: 200 million people worldwide are chronically infected and are at risk for the development of hepatocellular carcinoma. The source of HCV is unknown because there are no closely related animal virus homologs, but the hunt for related viruses has focused mainly on nonhuman primates. The identification of a related virus was fortuitous, and came about during a study of respiratory viruses that infect dogs. Nasal swabs were obtained from dogs with respiratory illness in shelters in Texas, Utah, and Pennsylvania. Sequence analysis of viral nucleic acids revealed the presence of a virus related to HCV, which was named canine hepacivirus (CHV). The virus was found in respiratory samples from 6 of 9 and 3 of 5 dogs in two separate outbreaks of respiratory disease, but not in 60 healthy pet dogs.
CHV was present in liver, but not lung, of 5 dogs that had died from unexplained gastrointestinal illness. The amount of CHV RNA in respiratory samples was substantially higher than in liver. Viral RNA was detected in the cytoplasm of hepatocytes in canine liver, but whether CHV is hepatotropic (replicates in liver cells) in dogs is not known. In humans, the amount of HCV in respiratory samples is typically very low. CHV may therefore infect different cells and tissues in dogs than does HCV in humans.
Bioinformatic analysis of CHV revealed that it is the genetically more related to HCV than any other known virus. HCV and CHV probably shared a common ancestor that circulated between 500 and 1,000 years ago – many years after dogs were domesticated. It is possible that hepaciviruses are mainly dog viruses, and that HCV arose by transmission of the virus from a dog to a human. An alternative scenario that cannot be excluded is that hepaciviruses infect many animal species. Screening of other animals for the presence of hepaciviruses must be done to determine which hypothesis is correct.
It was not possible to infect canine cultured cells with CHV, using clinical specimens from dogs. The reason for this failure is not known, but could mean that the cells used are not susceptible and/or permissive for viral replication. Furthermore, a full-length DNA copy of the viral genome, which could be used to produce infectious viral RNA, was not reported. Propagation of the virus in cell cultures will be essential for enabling research on CHV replication and pathogenesis.
The discovery of CHV is exciting because the virus provides clues about the origins of HCV and will likely stimulate a search for related viruses in other animals. It is possible that CHV infection of dogs might be a model for understanding the pathogenesis of HCV, which currently is only possible in chimpanzees. A convenient animal model would be valuable for devising new ways to prevent and treat HCV infections.
A. Kapoor, P. Simmonds, G. Gerold, N. Qaisar, K. Jain, J.A. Henriquez, C. Firth, D.L. Hirschberg, C. Rice, S. Shields, & W.I. Lipkin. (2011). Characterization of a canine homolog of hepatitis C virus Proc. Natl. Acad. Sci. USA
Although I’m sure there’s a good reason to disqualify this possibility, why can’t HCV be a human specific pathogen that transferred over to dogs? You don’t specifically mention this possibility, so I’m genuinely curious.
This is very interesting! I wonder if there’s a panel of canine cell types that could be screened for entry/replication of CHV. I’m not familiar with canine cell types, but I know we used this method to determine the receptor and cell type that Dengue virus prefers. What a great PhD project!
-Brooke (smallerquestions.org)
It’s a good question. I asked Amit Kapoor, first author of the paper, and he said the possibility of human to canine transmission can’t be ruled out, but it’s not likely. A respiratory virus (CHV) infecting its non-natural host (human) is more likely than a transmission restricted/transfusion transmitted virus (HCV) jumping into canines. If viruses similar to CHV are found in other animal species this would confirm its zoonotic origin.
HCV and CHV probably shared a common ancestor that circulated between 500 and 1,000 years ago is speculative. The first recorded evidence of HCV was found in serum samples saved by the Military during a 1942 hepatitis B outbreak among troops after receiving vaccines made from blood products. The late 1950 thru the 1960 decade, industry stopped heating blood products causing the explosion of the HCV epidemic.  Therefore it is not unreasonable to assume the same process for preparing animal vaccinations were also used…. for immune globulin based products such as rabies.  CHV may therefore infect different cells and tissues in dogs than does HCV in humans is not quite true either. Studies show that HCV infects not only liver, but lymphocytes blood cells, the lung, brain, spinal and heart cells. For patients that have been “cured”, active virus has been identified in all organs. A google search will verify this information or visit http://hcvets.com/data/hcv_liver/extra_hepatic_and_other_manifest.htm HCV is not just a hepacivirus in the family Flaviviridae but more closely related to the Dengue virus.
What is most speculative is to say that HCV is more closely related to Dengue.
Reverse zoonosis can’t be ruled out
now. It will be interesting to see if subsequent studies will find existence of
CHV-HCV like viruses in dog related species like wolf, foxes etc. that are not in direct
human contact.
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Alex Ling raises a very good point – why not look at it from the angle that humans trasferred HCV over to canines?
I asked the first author to answer your question. Here is his reply:
It can’t be ruled out now – but if subsequent studies report existence
of similar viruses in dog related species (no study done) it will
confirm its zoonotic origin. What we know is that several groups
studied species close to humans and found nothing similar to HCV.
Moreover non-primate relatives of other human virus like GBV-C, HIV,
TTV are known (Fig-4).
Another important point is WHAT one considers as long term successful
host-virus relationship? A pathogenic virus with inefficient
transmission (only blood borne) or a non-/weakly pathogenic virus with
transmission possible by the easiest means (aerosol). Moreover, a well
host adapted virus is one that will not end its host in all instances
(polio kills 1-1000).
Also a respiratory virus (CHV) jumping into its non-natural host
(Human) is more likely than a transmission restricted/transfusion
transmitted virus (HCV) jumping into canines.
I asked the first author to answer your question. Here is his reply:
It can’t be ruled out now – but if subsequent studies report existence
of similar viruses in dog related species (no study done) it will
confirm its zoonotic origin. What we know is that several groups
studied species close to humans and found nothing similar to HCV.
Moreover non-primate relatives of other human virus like GBV-C, HIV,
TTV are known (Fig-4).
Another important point is WHAT one considers as long term successful
host-virus relationship? A pathogenic virus with inefficient
transmission (only blood borne) or a non-/weakly pathogenic virus with
transmission possible by the easiest means (aerosol). Moreover, a well
host adapted virus is one that will not end its host in all instances
(polio kills 1-1000).
Also a respiratory virus (CHV) jumping into its non-natural host
(Human) is more likely than a transmission restricted/transfusion
transmitted virus (HCV) jumping into canines.
Thanks for this post about canine hepacivirus and its’ possible relationship to the hepatitis C virus. Â Intriguing information.
I have a question I would like to ask you.  I work closely with dogs.  Recently, I have been diagnosed with  Hepatitis C.  I have never had blood contact with any human.  I do not “use needle drugs” .  However, the research about canine HCV intrigues me because before I became sick, I was cleaning a dog’s crate and his feces entered an open wound on my finger, which caused my finger to swell for about a week, then a few months later I was diagnosed with this.  I know everything says the virus can’t jump from species.  The dog lives with me now and I noticed today he has a runny nose.  He is also underweight and has had some urinary tract infections.  Mainly, I want to be sure that he does not have HCV and to know how to treat him if he does.  How can I get a swab of his nasal discharge to a facility that can test him? Please respond to drusilla1128@gmail.com