A systematic review of reported reassortant viral lineages of influenza A

BACKGROUND: Most previous evolutionary studies of influenza A have focussed on genetic drift, or reassortment of specific gene segments, hosts or subtypes. We conducted a systematic literature review to identify reported claimed reassortant influenza A lineages with genomic data available in GenBank, to obtain 646 unique first-report isolates out of a possible 20,781 open-access genomes. RESULTS: After adjusting for correlations, only: swine as host, China, Europe, Japan and years between 1997 and 2002; remained as significant risk factors for the reporting of reassortant viral lineages. For swine H1, more reassortants were observed in the North American H1 clade compared with the Eurasian avian-like H1N1 clade. Conversely, for avian H5 isolates, a higher number of reported reassortants were observed in the European H5N2/H3N2 clade compared with the H5N2 North American clade. CONCLUSIONS: Despite unavoidable biases (publication, database choice and upload propensity) these results synthesize a large majority of the current literature on novel reported influenza A reassortants and are a potentially useful prerequisite to inform further algorithmic studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-015-1298-9) contains supplementary material, which is available to authorized users

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections.

Arenaviruses are one of the largest families of human hemorrhagic fever viruses and are known to infect both mammals and snakes. Arenaviruses package a large (L) and small (S) genome segment in their virions. For segmented RNA viruses like these, novel genotypes can be generated through mutation, recombination, and reassortment. Although it is believed that an ancient recombination event led to the emergence of a new lineage of mammalian arenaviruses, neither recombination nor reassortment has been definitively documented in natural arenavirus infections. Here, we used metagenomic sequencing to survey the viral diversity present in captive arenavirus-infected snakes. From 48 infected animals, we determined the complete or near complete sequence of 210 genome segments that grouped into 23 L and 11 S genotypes. The majority of snakes were multiply infected, with up to 4 distinct S and 11 distinct L segment genotypes in individual animals. This S/L imbalance was typical: in all cases intrahost L segment genotypes outnumbered S genotypes, and a particular S segment genotype dominated in individual animals and at a population level. We corroborated sequencing results by qRT-PCR and virus isolation, and isolates replicated as ensembles in culture. Numerous instances of recombination and reassortment were detected, including recombinant segments with unusual organizations featuring 2 intergenic regions and superfluous content, which were capable of stable replication and transmission despite their atypical structures. Overall, this represents intrahost diversity of an extent and form that goes well beyond what has been observed for arenaviruses or for viruses in general. This diversity can be plausibly attributed to the captive intermingling of sub-clinically infected wild-caught snakes. Thus, beyond providing a unique opportunity to study arenavirus evolution and adaptation, these findings allow the investigation of unintended anthropogenic impacts on viral ecology, diversity, and disease potential

The potential for reassortment between Oropouche and Schmallenberg Orthobunyaviruses

A number of viruses within the Peribunyaviridae family are naturally occurring reassortants, a common phenomenon for segmented viruses. Using a minigenome-reporter and virus-like particle (VLP) production assay, we have accessed the potential of Oropouche virus (OROV), Schmallenberg virus (SBV), and other orthobunyaviruses within the Simbu serogroup to reassort. We found that the untranslated region (UTR) in the medium segment is a potential contributing factor for reassortment by the tested viruses. We demonstrate that for promoter activity to occur it was essential that the viral RNA polymerase (L) and nucleocapsid (N) proteins were from the same virus, reinforcing the hypothesis that the large and small segments that encode these proteins segregate together during genome reassortment. Our results indicate that, given the right epidemiological setting, reassortment between SBV and OROV would potentially be feasible and could contribute to the emergence of a new Simbu virus

Genetic analysis of members of the species Oropouche virus and identification of a novel M segment sequence

Oropouche virus (OROV) is a public health threat in South America, and in particular Northern Brazil, causing frequent outbreaks of febrile illness. Using a combination of deep sequencing and Sanger sequencing approaches we have determined complete genome sequences of eight clinical isolates that were obtained from patient sera during an Oropouche fever outbreak in Amapa state, northern Brazil in 2009. We also report complete genome sequences of two OROV reassortants isolated from two marmosets in Minas Gerais state, southeast Brazil in 2012 that contain a novel M genome segment. Interestingly, all ten isolates posses a 947 nucleotide long S segment that lacks 11 residues in the S segment 3' UTR compared to the recently redetermined Brazilian prototype OROV strain BeAn19991. OROV maybe circulating more widely in Brazil and in the non-human primate population than previously appreciated and the identification of yet another reassortant highlights the importance of bunyavirus surveillance in South America

Oropouche virus: clinical, epidemiological, and molecular aspects of a neglected orthobunyavirus.

Oropouche virus (OROV) is an important cause of arboviral illness in Latin American countries, more specifically in the Amazon region of Brazil, Venezuela and Peru, as well as in other countries such as Panama. In the past decades, the clinical, epidemiological, pathological, and molecular aspects of OROV have been published and provide the basis for a better understanding of this important human pathogen. Here, we describe the milestones in a comprehensive review of OROV epidemiology, pathogenesis, and molecular biology, including a description of the first isolation of the virus, the outbreaks during the past six decades, clinical aspects of OROV infection, diagnostic methods, genome and genetic traits, evolution, and viral dispersal

Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus

The source, timing, and geographical origin of the 1918–1920 pandemic influenza A virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among young adults. Here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal H1N1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. Our results suggest that the 1918 pandemic virus originated shortly before 1918 when a human H1 virus, which we infer emerged before ∼1907, acquired avian N1 neuraminidase and internal protein genes. We find that the resulting pandemic virus jumped directly to swine but was likely displaced in humans by ∼1922 by a reassortant with an antigenically distinct H1 HA. Hence, although the swine lineage was a direct descendent of the pandemic virus, the post-1918 seasonal H1N1 lineage evidently was not, at least for HA. These findings help resolve several seemingly disparate observations from 20th century influenza epidemiology, seroarcheology, and immunology. The phylogenetic results, combined with these other lines of evidence, suggest that the highmortality in 1918 among adults aged ∼20 to ∼40 y may have been due primarily to their childhood exposure to a doubly heterosubtypic putative H3N8 virus, which we estimate circulated from ∼1889–1900. All other age groups (except immunologically naive infants) were likely partially protected by childhood exposure to N1 and/or H1-related antigens. Similar processes may underlie age-specific mortality differences between seasonal H1N1 vs. H3N2 and human H5N1 vs. H7N9 infections

Alvira : comparative genomics of viral strains

The Alvira tool is a general purpose multiple sequence alignment viewer with a special emphasis on the comparative analysis of viral genomes. This new tool has been devised specifically to address the problem of the simultaneous analysis of a large number of viral strains. The multiple alignment is embedded in a graph that can be explored at different levels of resolution