title: Biased mutational pattern and quasispecies hypothesis in H5N1 virus.
abstract: Like other RNA viruses, influenza viruses are subject to high mutation rates. Carrying segmented RNA genomes, their genetic variability is even higher. We aimed at analyzing the mutational events occurring during the infection of chickens by the Highly Pathogenic Avian Influenza (HPAI) H5N1 virus. We therefore studied the different sequences of two surface proteins, hemagglutinin (HA) and neuraminidase (NA), as well as two internal proteins, PB2 and NS. Three organs (lung, spleen, brain) were obtained from a chicken, experimentally infected with a lethal dose of HPAI H5N1 virus. Cloning these PCR fragments enabled us to investigate the mutations undergone by the virus after several replicative cycles. The first outcome is the presence of a strong mutational bias, resembling host-driven ADAR1 adenosine deamination, which is responsible for 81% of all mutations. Whereas the frequency of RNA dependent RNA polymerase-related mutations is compatible with the survival of the virus, the ADAR1-like activity usually strongly increases the mutation frequency into a level of "error catastrophe" in theory incompatible with virus survival. Nevertheless, the virus was successfully infective. HPAI H5N1 virus displayed traits in agreement with the quasispecies theory. The role of this quasispecies structure in successful infection and the superposition with the ADAR1-like response is discussed.
authors: Virology Unit, Institut Pasteur in Cambodia, Réseau International des Instituts Pasteur, 5 Monivong blvd, PO Box 983, Phnom Penh, Cambodia.
authors: Ramona Alikiiteaga
authors: RA
authors: Gutiérrez
authors: Alain
authors: A
authors: Viari
authors: Bernard
authors: B
authors: Godelle
authors: Roger
authors: R
authors: Frutos
authors: Philippe
authors: P
authors: Buchy
mesh_terms: D000818:Animals; D002645:Chickens / Q000821:virology; D004252:DNA Mutational Analysis; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000235:genetics*; D005585:Influenza in Birds / Q000821:virology*; D009154:Mutation; D059645:Mutation Rate; D010802:Phylogeny; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins