When we talk about influenza viruses, Influenza A and Influenza B pretty much capture all of the headlines. Less well known are the Influenza C viruses - which while less common - circulate both in humans and in swine.
For those looking for a detailed virology lesson, Vincent Racaniello wrote about the three types of influenza viruses in 2009 on his Virology Blog in a piece called The A, B, and C of influenza virus.
Although most adults have encountered the influenza C virus at least once in their life, it tends to produce only mild upper respiratory tract infections. The CDC describes influenza B & C viruses this way.
Influenza Type B
Influenza B viruses are usually found only in humans. Unlike influenza A viruses, these viruses are not classified according to subtype. Influenza B viruses can cause morbidity and mortality among humans, but in general are associated with less severe epidemics than influenza A viruses. Although influenza type B viruses can cause human epidemics, they have not caused pandemics.
Influenza Type C
Influenza type C viruses cause mild illness in humans and do not cause epidemics or pandemics. These viruses are not classified according to subtype.
Our knowledge of influenza C is somewhat limited, but last December, Lisa Schnirring at CIDRAP NEWS wrote this report on a study of Influenza C viruses.
Lisa Schnirring Staff Writer
Dec 7, 2012 (CIDRAP News) – Influenza C generally isn't thought to be a cause clinically significant disease, but a study in Italian children who were seen in the emergency department for pneumonia found the virus in five children, with a disease severity that resembled influenza A.
The study evaluated data from four flu seasons from 2008-09 to 2011-12 at a pediatric clinic in Milan and appeared today in an early online edition of Influenza and Other Respiratory Viruses.
Influenza B and C are considered unlikely to have much in the way of pandemic potential because they lack the multiple sub-types found with influenza A viruses (17 hemagglutinin and 9 neuraminidase subtypes) that allow for viral reassortment.
Two Influenza A viruses can swap genetic segments to produce new hybrid (reassortant) viruses.
But of course, one should never say `never’. . . .
From PloS Pathogens today we get the first study to suggest that influenza C viruses might have the ability to reassort and evolve at a rate that could pose a greater threat than previously believed.
The study is called:
Isolation of a Novel Swine Influenza Virus from Oklahoma in 2011 Which Is Distantly Related to Human Influenza C Viruses
Ben M. Hause , Mariette Ducatez, Emily A. Collin, Zhiguang Ran, Runxia Liu, Zizhang Sheng, Anibal Armien, Bryan Kaplan, Suvobrata Chakravarty, Adam D. Hoppe, Richard J. Webby, Randy R. Simonson, Feng Li
EXCERPTS (slightly reparagraphed)
Of the Orthomyxoviridae family of viruses, only influenza A viruses are thought to exist as multiple subtypes and has non-human maintenance hosts.
In April 2011, nasal swabs were collected for virus isolation from pigs exhibiting influenza-like illness. Subsequent electron microscopic, biochemical, and genetic studies identified an orthomyxovirus with seven RNA segments exhibiting approximately 50% overall amino acid identity to human influenza C virus.
Based on its genetic organizational similarities to influenza C viruses this virus has been provisionally designated C/Oklahoma/1334/2011 (C/OK). Phylogenetic analysis of the predicted viral proteins found that the divergence between C/OK and human influenza C viruses was similar to that observed between influenza A and B viruses.
No cross reactivity was observed between C/OK and human influenza C viruses using hemagglutination inhibition (HI) assays.
Additionally, screening of pig and human serum samples found that 9.5% and 1.3%, respectively, of individuals had measurable HI antibody titers to C/OK virus. C/OK virus was able to infect both ferrets and pigs and transmit to naive animals by direct contact.
Cell culture studies showed that C/OK virus displayed a broader cellular tropism than a human influenza C virus. The observed difference in cellular tropism was further supported by structural analysis showing that hemagglutinin esterase (HE) proteins between two viruses have conserved enzymatic but divergent receptor-binding sites.
These results suggest that C/OK virus represents a new subtype of influenza C viruses that currently circulates in pigs that has not been recognized previously. The presence of multiple subtypes of co-circulating influenza C viruses raises the possibility of reassortment and antigenic shift as mechanisms of influenza C virus evolution.
Influenza C viruses infect most humans during childhood. Unlike influenza A viruses, influenza C viruses exhibit little genetic variability and evolve at a comparably slower rate. Influenza A viruses exist as multiple subtypes and cause disease in numerous mammals.
In contrast, influenza C viruses are comprised of a single subtype in its primary human host. Here we characterize a novel swine influenza virus, C/swine/Oklahoma/1334/2011 (C/OK), having only modest genetic similarity to human influenza C viruses. No cross-reaction was observed between C/OK and human influenza C viruses.
Antibodies that cross react with C/OK were identified in a significant number of swine but not human sera samples, suggesting that C/OK circulates in pigs. Additionally, we show that C/OK is capable of infecting and transmitting by direct contact in both pigs and ferrets.
These results suggest that C/OK represents a new subtype of influenza C viruses. This is significant, as co-circulation of multiple subtypes of influenza allows for rapid viral evolution through antigenic shift, a property previously only shown for influenza A viruses.
The ability of C/OK to infect ferrets along with the absence of antibodies to C/OK in humans, suggests that such viruses may become a potential threat to human health.
This is a fascinating paper, well worth exploring in its entirety.
How much of a threat influenza C viruses really pose is something that needs to be established, but once again we are reminded that our understanding of the world of influenza viruses – while continually expanding – remains far from complete.