New viruses 2009

They shed the virus and readily transmit it between themselves, but whereas S-OIV has been reported in humans worldwide, it has not yet been reported from a pig farm in the USA October By contrast it has been found in two piggeries each in Australia, Canada and Ireland, and one each in Argentina, Indonesia and Japan.

In the outbreaks in Argentina, Australia and Canada, at least, the pigs had not been vaccinated Jorge H. Dillon, J.

Keenliside and Alain Laperle, personal communication , and became infected from infected farm staff. Circumstantial evidence must always be treated with caution. One major uncertainty in trying to determine the origin of S-OIV is that one cannot predict which characters of the parental viruses have remained or changed during the reassortment process that produced S-OIV.

If, for example, the significant infectiousness of S-OIV is an 'emergent' property of S-OIV, and not shown by its parents, then one could conclude that the final reassortment probably occurred at about the time it emerged in early However it is not yet known whether S-OIV's infectiousness is novel; the reassortment may have occurred a decade ago, and a recent mutation may have enhanced its infectiousness.

Another widely reported feature of S-OIV is that it replicates poorly in embryonated eggs, but again this may be merely a specific feature of S-OIV and not its immediate parents.

Similarly the fact that the evolutionary rate of all of the genes of S-OIV seem to be 'normal' during their unsampled pre-emergent period [ 8 , 11 ]] does not prove that the virus or its parents have been maintained in "unsampled" pig herds and precluded the possibility of human involvement, as viruses grown for vaccines evolve, and indeed might be expected to show an increased evolutionary rate [ 32 , 33 ] while adapting to eggs, a new host, although such an increase may have been offset by the practice of storing 'seed stocks' for use in several 'production cycles' in vaccine production, so that the evolutionary age of a vaccine virus may be less than its sidereal age, and the average could then appear to be 'normal'.

Finally there is the report that the first human S-OIV infections were in Perote, a small Mexican town with a very large number of large piggeries, although it was also reported that none of the pigs showed signs of influenza. Among the earliest cases were some in Oaxaca, kms to the south [ 34 ].

Perote is an unlikely place for an infected migratory pig to arrive from an intercontinental trip, as the town is in a remote high valley surrounded by mountains, kms to the east of Mexico City where there is the nearest major airport, and kms from the nearest port at Vera Cruz. The four month difference between 'The Most Recent Common Ancestor' date for S-OIV estimated from its phylogeny [ 8 , 11 ], and its earliest detection in the human population makes it more difficult to make specific conclusions about its provenance.

We have also checked whether any extra information about the origin of S-OIV can be gleaned from gene sequence features reported to be associated with host adaptation, virulence, etc. Such sequence signatures must be interpreted with caution as although Genbank records the source host of influenza isolates, it rarely records their passage hosts and passage history.

Influenza viruses are nowadays mostly isolated in MDCK cells, but early influenza isolates were mostly grown in embryonated hen's eggs, and adaptation to eggs is known to cause protein sequence changes [ 32 , 33 , 35 , 36 ]. Therefore we compared sequence signatures and motifs in S-OIV with those of their closest relatives. Subbarao and his colleagues [ 37 ] were first to show that amino acid of the PB2 protein was almost always glutamate in bird isolates and lysine in human isolates.

Chen and colleagues [ 38 ] made a much more extensive survey of sequences and found 51 more sites in 10 of the 11 proteins of influenza virus that discriminated between bird and human isolates as well as, or better than, PB At 29 of the sites, the amino acids of the 'S-OIV cluster' i.

S-OIV and the swine viruses closest to it are avian-like, at 16 they are human-like, at 6 in the matrix proteins they are novel, and the single recognised site in some NS1s has been lost by truncation.

However, surprisingly, all the five recognised sites in the PB1-F2 protein of the S-OIV cluster have human-like residues, whereas the other 11 human-like residues are spread over 40 sites in eight proteins. In most influenza viruses the PB1 gene encodes three proteins [ 39 , 40 ]. In a small number of influenzas, including all S-OIVs, the PB1-F2 ORF is truncated by termination codons at positions 12, 58 and 88, and its absence is associated with avirulence in mice [ 41 - 43 ].

Trifonov and colleagues have reported statistical tests of various features of the PB1-F2 region [ 26 ], and concluded "that PB1-F2 is of little or no evolutionary significance for the virus". It seems that the peculiarities of the S-OIV PB1-F2 gene, the human-like signature sites and its selectively super-imposed termination codons, probably reflect the outcome of selection rather than being of "little or no evolutionary significance".

Finally, we examined the NS1 protein, which in c. Thus our examination of sequence signatures and motifs in the S-OIV genome has not clarified our knowledge of its origins, but has certainly raised many new questions. Public confidence in influenza research, and the agribusinesses that are based on influenza's many hosts, has been eroded by several recent events. Measures that might restore confidence include establishing both a unified international administrative framework coordinating all surveillance, research and commercial work with this virus, and also a detailed registry of all influenza isolates held for research and vaccine production.

The phylogenetic information presently available does not identify the source of S-OIV, however it provides some clues, which can be translated into hypotheses of where and how it might have originated. Two contrasting possibilities have been described and discussed in this commentary, but more data are needed to distinguish between them. It would be especially valuable to have gene sequences of isolates filling the time and phylogenetic gap between those of S-OIV and those closest to it.

We believe that these important sequences are most likely to be found in isolates from as-yet-unsampled pig populations or as-yet-unsampled laboratories, especially those holding isolates of all three clusters of viruses closest to those of S-OIV, and involved in vaccine research and production.

Quarantine and trade records of live pigs entering North America could probably focus the search for the unsampled pig population. It is likely that further information about S-OIV's immediate ancestry will be obtained when the unusual features of its PB1-F2 gene are understood.

The work reported here was unfunded, and the authors have no competing financial or intellectual property interests. The work was planned as a result of discussions and projects involving all the authors. Analyses were done by AJG, all authors contributed to the manuscript. Taxonomic methods and sequence Accession Codes. National Center for Biotechnology Information , U.

Journal List Virol J v. Virol J. Published online Nov Author information Article notes Copyright and License information Disclaimer. Corresponding author. Adrian J Gibbs: moc. Received Jul 29; Accepted Nov This article has been cited by other articles in PMC. DOC 50K. Abstract The swine-origin influenza A H1N1 virus that appeared in and was first found in human beings in Mexico, is a reassortant with at least three parents.

Introduction A novel H1N1 influenza virus, Swine-Origin Influenza Virus S-OIV , was first isolated in mid-April and, by the end of the month, the first complete genomic sequences were published, and the virus shown to be of a novel re-assortant [ 1 ].

Discussion Phylogenetic Studies One of the most intriguing findings of the phylogenetic studies is that each S-OIV gene is connected to its respective phylogenetic tree by a noticeably long branch. Become an underwriter». All rights reserved. The University of Minnesota is an equal opportunity educator and employer.

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Avian Influenza Bird Flu. H1N1 Pandemic Influenza. Influenza, General. Pandemic Influenza. Public Health. Jun 25, The Kupe virus titer increased more rapidly than the DUGV titers and achieved peak titers 1—2 days earlier. The subsequent decrease in titer was also more rapid Figure 1. However, in all but LLC-MK 2 cells, Kupe virus caused greater overall destruction of the cell monolayer by the end of the growth curve experiment.

In Vero cell plaque assays, DUGV plaques were slower to form than those caused by Kupe virus, although plaque morphology of the 2 viruses was similar 2—4 mm in diameter. The 3 genomic RNA segments of Kupe virus, isolate K, were completely sequenced, ORFs were identified, and deduced amino acid sequences were determined.

As observed in other nairoviruses, the Kupe virus M ORF, which has 1, aa, is longer than those of other members of Bunyaviridae 9 , Kupe virus contains a unique potential N-gly site in the Gn and Gc glycoprotein regions aa and aa and was missing potential sites found at aa 30, 80, , and in DUGV.

Further analysis is necessary to determine which of the potential N-gly sites are used in DUGV and Kupe virus proteins. The Kupe virus ORF aa sequence shows a high degree of homology to that of DUGV, with the exception of a highly variable region Kupe virus aa — that shows low homology Figure 2.

Phylogenetic trees produced by using maximum-parsimony analysis with bootstrap replicates on alignments of full-length amino acid sequences of the A small segment, B medium segment, and C large segment of Nucleotide and deduced amino acid sequences of Kupe virus segments were compared with sequences from other nairoviruses available in GenBank and with partial sequences of DUGV isolates obtained in the Kenya survey in which Kupe virus was isolated Tables 3 — 6 3.

Comparison of full-length S segment sequences showed Identities among the 5 DUGV strain sequences were nt A nt fragment of the S segment, corresponding to Kupe S nt 44—, was also sequenced from 26 DUGV isolates obtained during the abattoir survey GenBank accession nos.

Results of these comparisons are shown in Table 6. Nucleotide and amino acid sequence identities among 5 Kupe virus isolates for a nt fragment nt — of the S segment were Results of phylogenetic analysis of the full-length S segment amino acid sequence alignment is shown in Figure 2 , panel A. Comparison of these viruses with Kupe virus M segment sequence showed Sequence identities between 5 Kupe virus isolates for a 1,nt fragment of the M segment nt — were Phylogenetic analysis of full-length M segment amino acid sequences resulted in a tree with topology similar to that of the S segment tree Figure 2 , panel B.

Comparison of these sequences with Kupe virus sequence showed As expected from this data, phylogenetic analysis of full-length L segment aa sequence resulted in a tree showing Kupe virus more closely related to Dugbe virus than in the S or M segment trees Figure 2 , panel C. Figure 3. Phylogenetic tree produced by using maximum parsimony analysis with bootstrap replicates on amino acid alignment of nairovirus large segment fragment aa sequence translated from nt sequence.

Scale bar Nucleotide and amino acid sequence comparisons of a nt fragment of the highly conserved L segment RDRP catalytic core domain Kupe virus nt — were also made between Kupe virus and sequences of 14 other viruses representing 7 groups of the Nairovirus genus published by Honig et al. A phylogenetic tree derived from the amino acid alignment of these sequences shows Kupe virus most closely related to DUGV Sequence identities among 5 Kupe virus isolates for this fragment were nt Although little genetic information is available for most viruses in the genus Nairovirus , current classification of the diverse group of viruses in the genus is in relative agreement with available genetic analyses 19 , Genetic information is useful in identifying emerging viruses and in analysis of relationships between viruses, especially given the segmented nature of the nairovirus genome, which can lead to generation of new viruses by segment reassortment Within the genus, however, limited species and strain comparisons are available, making the definition of a genetic classification criteria difficult, and the segmented nature of the genome confounds the analysis.

These findings are shown by a recent in-depth genetic analysis of CCHFV strains that demonstrated a high degree of genomic plasticity and RNA segment reassortment among virus strains studied These lower identities, combined with differences observed in the L segment variable region Kupe virus aa — , suggest otherwise. Little is known about the ecology of Kupe virus other than its isolation from ticks infesting cattle.

DUGV has been reportedly isolated from several tick species, including A. Specific vector competence studies will be needed to resolve this point. Flu viruses are constantly changing called antigenic drift — they often change from one season to the next or they can even change within the course of one flu season. Experts must pick which viruses to include in the vaccine many months in advance in order for vaccine to be produced and delivered on time.

For more information about the seasonal flu vaccine virus selection process, visit Selecting the Viruses in the Influenza Flu Vaccine. Because of these factors, there is always the possibility of a less than optimal match between circulating flu viruses and the viruses in the seasonal flu vaccine. Because there were few seasonal flu viruses as opposed to H1N1 viruses in circulation during the season, vaccine effectiveness VE studies could not be performed for the seasonal vaccine.

The season was very unusual. The emergence of a new and very different H1N1 virus meant that two vaccines were needed: one to prevent seasonal influenza viruses that were anticipated to spread and another to prevent influenza caused by the newly emerged H1N1 virus. As usual, components of the seasonal flu vaccine were decided upon well in advance of the season and vaccine production was well underway by the time the new H1N1 virus emerged. If the H1N1 virus had emerged sooner, it would have been included in the seasonal vaccine.

Therefore, a second flu vaccine was created to protect against the new flu virus. The seasonal flu vaccine will protect against the H1N1 virus and 2 other flu viruses. Antiviral resistance means that a virus has changed in such a way that antiviral drugs have become less effective in treating or preventing illnesses caused by the virus. Samples of viruses collected from around the United States and the world are studied to determine if they are resistant to any of the four FDA-approved influenza antiviral drugs.

CDC routinely collects viruses through a domestic and global surveillance system to monitor for changes in influenza viruses.