Codon usage bias and the evolution of influenza A viruses. Codon Usage Biases of Influenza Virus

<p>Abstract</p> <p>Background</p> <p>The influenza A virus is an important infectious cause of morbidity and mortality in humans and was responsible for 3 pandemics in the 20^thcentury. As the replication of the influenza virus is based on its host's machinery, codon usage of its viral genes might be subject to host selection pressures, especially after interspecies transmission. A better understanding of viral evolution and host adaptive responses might help control this disease.</p> <p>Results</p> <p>Relative Synonymous Codon Usage (RSCU) values of the genes from segment 1 to segment 6 of avian and human influenza viruses, including pandemic H1N1, were studied via Correspondence Analysis (CA). The codon usage patterns of seasonal human influenza viruses were distinct among their subtypes and different from those of avian viruses. Newly isolated viruses could be added to the CA results, creating a tool to investigate the host origin and evolution of viral genes. It was found that the 1918 pandemic H1N1 virus contained genes with mammalian-like viral codon usage patterns, indicating that the introduction of this virus to humans was not through <it>in toto </it>transfer of an avian influenza virus.</p> <p>Many human viral genes had directional changes in codon usage over time of viral isolation, indicating the effect of host selection pressures. These changes reduced the overall GC content and the usage of G at the third codon position in the viral genome. Limited evidence of translational selection pressure was found in a few viral genes.</p> <p>Conclusions</p> <p>Codon usage patterns from CA allowed identification of host origin and evolutionary trends in influenza viruses, providing an alternative method and a tool to understand the evolution of influenza viruses. Human influenza viruses are subject to selection pressure on codon usage which might assist in understanding the characteristics of newly emerging viruses.</p

Heterologous influenza vRNA segments with identical non-coding sequences stimulate viral RNA replication in trans

The initiation of transcription and replication of influenza A virus requires the 5' and 3' ends of vRNA. Here, the role of segment-specific non-coding sequences of influenza A virus on viral RNA synthesis was studied. Recombinant viruses, with the nonstructural protein (NS) segment-specific non-coding sequences replaced by the corresponding sequences of the neuraminidase (NA) segment, were characterized. The NS and NA vRNA levels in cells infected with these mutants were much higher than those of the wild type, whereas the NS and NA mRNA levels of the mutants were comparable to the wild-type levels. By contrast, the PB2 vRNA and mRNA levels of all the tested viruses were similar, indicating that vRNA with heterologous segment-specific non-coding sequences was not affected by the mutations. The observations suggested that, with the cooperation between the homologous 5' and 3'segment-specific sequences, the introduced mutations could specifically enhance the replication of NA and NS vRNA

In-Flight Transmission of SARS-CoV-2.

Four persons with severe acute respiratory syndrome coronavirus 2 infection had traveled on the same flight from Boston, Massachusetts, USA, to Hong Kong, China. Their virus genetic sequences are identical, unique, and belong to a clade not previously identified in Hong Kong, which strongly suggests that the virus can be transmitted during air travel

DNA intercalator stimulates influenza transcription and virus replication

Influenza A virus uses its host transcription machinery to facilitate viral RNA synthesis, an event that is associated with cellular RNA polymerase II (RNAPII). In this study, various RNAPII transcription inhibitors were used to investigate the effect of RNAPII phosphorylation status on viral RNA transcription. A low concentration of DNA intercalators, such as actinomycin D (ActD), was found to stimulate viral polymerase activity and virus replication. This effect was not observed in cells treated with RNAPII kinase inhibitors. In addition, the loss of RNAPIIa in infected cells was due to the shift of nonphosphorylated RNAPII (RNAPIIa) to hyperphosphorylated RNAPII (RNAPIIo)

Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation

Amongst all the internal gene segments (PB2. PB1, PA, NP, M and NS), the avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis, we tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature. These viruses were potent inducers of proinflammatory cytokines and chemokines in primary human macrophages and pneumocytes. Viruses with this specific PB2-PB1 combination were also found to be more capable to generate adaptive mutations under a new selection pressure. These results suggested that the viral polymerase activity might be relevant for the genesis of influenza viruses of human health concern

Detection of highly pathogenic influenza and pandemic influenza virus in formalin fixed tissues by immunohistochemical methods

Tissues infected with highly pathogenic avian influenza viruses such as H5N1 and H7N7 are normally required to be fixed in formalin or paraformaldehyde before examination in order to inactivate the virus. In this study commercially available monoclonal antibodies to the influenza nucleoprotein (NP) were evaluated in order to determine which antibodies would identify positive cells in tissues fixed in formalin or paraformaldehyde. An assessment of which antigen retrieval process would unmask antigens blocked by formalin fixation was also made. Of six commercially available monoclonal antibodies tested, only one (HB65, European Veterinary Laboratories) was able to identify all formalin fixed avian, swine and human influenza virus infected tissues, and this was after pronase induced epitope retrieval. This monoclonal antibody is recommended for routine diagnostic use for the detection of influenza A infected tissues that have been fixed in formalin or paraformaldehyde. © 2011 Elsevier B.V.link_to_subscribed_fulltex