Abstract
Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1) multiple lineages have been circulating globally; (2) there have been weak and infrequent selective bottlenecks; (3) the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4) there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics.
Highlights
The influenza C virus is predominantly found in humans, and infection in humans can cause respiratory and febrile symptoms that are similar to those caused by influenza A and B viruses.Influenza C virus infections are generally mild and self-limited but can cause more severe lower respiratory tract illness, such as bronchitis and pneumonia [1,2]
Apart from antigenic analyses using viral isolates and sera or monoclonal antibodies against the viruses [17,36], phylogenetic analyses using genetic sequence data of the HE gene could provide important information about the evolution of the influenza C virus
Sequence data of the HA gene of human influenza A and B viruses were obtained from the Influenza Virus Resource database; we randomly selected a maximum of 20 strains per year for each dataset: A/H1N1, A/H3N2, and B
Summary
The influenza C virus is predominantly found in humans, and infection in humans can cause respiratory and febrile symptoms that are similar to those caused by influenza A and B viruses. The seasonal influenza A virus accumulates mutations in the hemagglutinin (HA) gene, which encodes a major surface antigenic protein of the virus [21,24]. Apart from antigenic analyses using viral isolates and sera or monoclonal antibodies against the viruses [17,36], phylogenetic analyses using genetic sequence data of the HE gene could provide important information about the evolution of the influenza C virus. Because isolation of the influenza C virus using cell cultures, such as MDCK and LLC-MK2 cells requires technical proficiency and intensive observation of inoculated cells, isolation of the virus is rarely performed This is one of the reasons why sequence data of the virus are still limited. We compared the evolution of influenza C viruses with those of influenza A and B viruses
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