Search PubMed⌕ Search

Biomedical subjects

K F Shortridge

Publications and source records attributed to K F Shortridge.

At least 55 records · Page 3Linked to original sources

Genetic reassortment in pandemic and interpandemic influenza viruses. A study of 122 viruses infecting humans.

The human influenza pandemics of 1957 and 1968 were caused by reassortant viruses that possessed internal gene segments from avian and human strains. Whether genetic reassortment of human and avian influenza viruses occurs during interpandemic periods and how often humans are infected with such reassortants is not known. To provide this information, we used dot-blot hybridization, partial nucleotide sequencing and subsequent phylogenetic analysis to examine the 6 internal genes of 122 viruses isolated in humans between 1933 and 1992 primarily from Asia, Europe, and the Americas. The internal genes of A/New Jersey/11/76 isolated from a human fatality at Fort Dix, New Jersey in 1976 were found to be of porcine origin. Although none of the geographically and temporally diverse collection of 122 viruses was an avian-human or other reassortant, cognizance was made of the fact that there were two isolates from children from amongst 546 influenza A isolates obtained from The Netherlands from 1989-1994 which were influenza A reassortants containing genes of avian origin, viruses which have infected European pigs since 1983-1985. Thus, genetic reassortment between avian and human influenza strains does occur in the emergence of pandemic and interpandemic influenza A viruses. However, in the interpandemic periods the reassortants have no survival advantage, and the circulating interpandemic influenza viruses in humans do not appear to accumulate avian influenza virus genes.

Base Sequence↗

Emergence of avian H1N1 influenza viruses in pigs in China.

Avian influenza A viruses from Asia are recognized as the source of genes that reassorted with human viral genes to generate the Asian/57 (H2N2) and Hong Kong/68 (H3N2) pandemic strains earlier in this century. Here we report the genetic analysis of avian influenza A H1N1 viruses recently isolated from pigs in southern China, a host suspected to generate new pandemic strains through gene reassortment events. Each of the eight gene segments was of avian origin. Phylogenetic analysis indicates that these genes form an Asian sublineage of the Eurasian avian lineage, suggesting that these viruses are an independent introduction into pigs in Asia. The presence of avian influenza viruses in pigs in China places them in an optimal position for transmission to humans and may serve as an early warning of the emergence of the next human influenza virus pandemic.

Animals↗

Outbreak of equine influenza among horses in Hong Kong during 1992.

Equine-2 influenza virus A (H3N8) infection occurred among vaccinated thoroughbred horses in Hong Kong during November and December 1992. The outbreak was unique in that it occurred among a large population stabled under intensive conditions. It resulted in the postponement of seven race meetings over a period of 32 days. The outbreak originated after the importation of horses 25 to 32 days before any clinical signs were reported. Vaccination did not prevent 75 per cent of the population from becoming infected, and half the infected horses developed clinical signs. Vaccination did, however, contribute to reducing the morbidity and the severity and duration of the clinical signs.

Animals↗

Genetic analysis of porcine H3N2 viruses originating in southern China.

From immunological and phylogenetic analyses of H3 influenza viruses isolated from pigs and ducks in the People's Republic of China (China), Hong Kong, Taiwan and Japan, between 1968 and 1982, we arrived at the following conclusions. The H3 haemagglutinin and N2 neuraminidase genes from swine isolates can be segregated into four mammalian lineages, including: (i) the earliest human strains; (ii) early swine strains including Hong Kong isolates from 1976-1977; (iii) an intermediate strain between the early swine and recent human strains; and (iv) recent human strains. In this study we found an unusual swine strain (sw/Hong Kong/127/82) belonging to the third lineage which behaved like those of the early swine-like lineage in the haemagglutination inhibition test; but neuraminidase inhibition profiles with monoclonal antibodies indicated that this virus is related to late human strains. On the basis of pairwise comparisons of complete or partial nucleotide sequences the genes encoding the three polymerase proteins (PB2, PB1, PA), the nucleoprotein, the membrane protein and possibly the nonstructural proteins of sw/Hong Kong/127/82 are of the swine H1N1 lineage, whereas genes encoding the two surface glycoproteins belong to the human H3N2 lineage. In contrast, all RNA segments of one swine isolate (sw/Hong Kong/81/78) are similar to those of recent human H3N2 viruses. This study indicated that frequent interspecies infections between human and swine hosts appeared to occur during 1976-82. Although the evolutionary rates of human (0.0122/site/year), swine (0.0127/site/year) and avian (0.0193/site/year) virus genes are similar when based upon synonymous substitutions, nonsynonymous substitutions indicated that viral genes derived from human and swine viruses evolved about three times faster (0.0026-0.0027/site/year) than those of avian viruses (0.0008/site/year). Furthermore, the evolutionary mechanism by which human and swine H3 haemagglutinin genes evolve at a similar rate, based on nonsynonymous substitutions, appeared to be quite different from previous evidence which showed that human H1 haemagglutinin genes evolved three times faster than those of swine viruses. However, comparison of the number of nonsynonymous substitutions in the antigenic sites (A-E) of haemagglutinin molecules demonstrated that swine viruses evolve at a rate that is about one fifth to one tenth that of human viruses, reflecting the conservative nature of the antigenic structure in the former.

Amino Acid Sequence↗

Genetic and antigenic analysis of the influenza virus responsible for the 1992 Hong Kong equine influenza epizootic.

An outbreak of influenza occurred among thoroughbred racehorses in Hong Kong in November-December 1992, with morbidity of 37%. All horses involved had been vaccinated against equine-1 and equine-2 influenza viruses but not against the virus responsible for the 1989 equine influenza outbreak in northern China (influenza A/equine/Jilin/89, subtype H3N8). Therefore the source and nature of the virus causing the Hong Kong outbreak was investigated. Virus isolated from a horse infected during the outbreak was used for genetic analysis. All the viral gene segments were similar to those of equine-2 (H3N8) influenza viruses and unrelated to those of equine/Jilin/89 virus. The nucleotide sequence of the viral hemagglutinin gene showed high homology (99.4%) to that of influenza A/equine/Suffolk/89 (H3N8) virus which has circulated extensively in Europe. However, these viruses differed in their antigenic reactivity to a panel of monoclonal antibodies. Preliminary epizootiological information plus the concordance of amino acid sequence between hemagglutinins of the Hong Kong isolate and a contemporaneous equine-2 influenza virus isolate from the United Kingdom indicated that the probable source of the Hong Kong outbreak was horses recently imported from England or Ireland.

Amino Acid Sequence↗

Rapid diagnosis of equine influenza by the Directigen FLU-A enzyme immunoassay.

The Directigen FLU-A enzyme immunoassay was tested for its ability to detect equine-2 influenza viruses in nasopharyngeal fluids from horses and ponies. A total of 125 swabs from experimental infections and from different sources of natural infection in the USA and Hong Kong were examined. The assay results were compared with the results of standard virus culture in embryonated chicken eggs or Madin-Darby canine kidney cells, and with the serology of the horses sampled. In comparison with virus culture the enzyme immunoassay exhibited 83 per cent sensitivity, 78 per cent specificity, 70 per cent positive predictive value and 88 per cent negative predictive value. The test appeared to be more sensitive than haemagglutination for the detection of low levels of virus in embryonated egg cultures. It also detected equine-1 influenza virus in culture. The test is rapid (15 minutes), simple, and should be a convenient method for the rapid diagnosis and screening of horses for equine influenza infection.

Animals↗

Evidence for interspecies transmission and reassortment of influenza A viruses in pigs in southern China.

The Asian/57, Hong Kong/68, and Russian/77 pandemics of this century appeared or reappeared in China. Interspecies transmission and genetic reassortment of influenza viruses have been implicated in the origin of these human pandemic influenza viruses. Pigs have been suspected to be the "mixing vessel" where reassortment occurs. To investigate this possibility, 104 porcine influenza viruses collected at random from Southern China from 1976 to 1982, including 32 H3N2 isolates and 72 H1N1 isolates, were studied using dot blot hybridization, partial sequencing, and phylogenetic analysis. There were 29 of 32 H3N2 isolates characteristic of viruses originally derived from humans; the other 3 isolates were reassortants containing genes from porcine and human influenza viruses. Phylogenetic analyses of the polymerase B1 (PB1) genes showed that interspecies transmission from humans to pigs has happened multiple times in pigs in Southern China. All 72 H1N1 isolates were of porcine origin characteristic of classical porcine H1N1 influenza virus. Analysis of 624 genes of porcine influenza viruses from Southern China failed to detect any evidence for avian influenza virus genes. This contrasts to what is currently found in Europe, where the majority of porcine influenza virus isolates are of avian origin.

Animals↗

Analysis of the influenza virus gene pool of avian species from southern China.

Although Southern China has been considered the epicenter of human influenza pandemics, little is known about the genetic composition of influenza viruses in lower mammals or birds in that region. To provide information on the molecular epidemiology of these viruses, we used dot blot hybridization and phylogenetic methods to study the internal genes (PB1, PB2, PA, NP, M, and NS) of 106 avian influenza A viruses isolated from a total of 11,798 domestic ducks, chickens, and geese raised in Southern China including Hong Kong. All 636 genes examined were characteristic of avian influenza viruses; no human or swine influenza genes were detected. Thus, influenza virus reassortants do not appear to be maintained in the domesticated birds of Southeast Asia, eliminating opportunities for further gene reassortment. Phylogenetic analysis showed that the internal genes of these viruses belong to the Eurasian avian lineage, supporting geographical separation of the major avian lineages. The PB1 genes were most similar to A/Singapore/57 (H2N2) and Hong Kong (H3N2) viral genes, supporting an avian origin for the recent human H2N2 and H3N2 pandemic strains. The majority of internal genes from avian influenza viruses in Southern China belong to the Eurasian lineage and are similar to viruses that have recently been transmitted to humans, swine, and horses. This study provides evidence that the transmission of avian influenza viruses and their genes to other species is unidirectional and that the transmission of mammalian influenza virus strains to domestic poultry is probably not a factor in the generation of new pandemic strains.

Animals↗

Origin and evolutionary pathways of the H1 hemagglutinin gene of avian, swine and human influenza viruses: cocirculation of two distinct lineages of swine virus.

The nucleotide sequences of the HA1 domain of the H1 hemagglutinin genes of A/duck/Hong Kong/36/76, A/duck/Hong Kong/196/77, A/sw/North Ireland/38, A/sw/Cambridge/39 and A/Yamagata/120/86 viruses were determined, and their evolutionary relationships were compared with those of previously sequenced hemagglutinin (H1) genes from avian, swine and human influenza viruses. A pairwise comparison of the nucleotide sequences revealed that the genes can be segregated into three groups, the avian, swine and human virus groups. With the exception of two swine strains isolated in the 1930s, a high degree of nucleotide sequence homology exists within the group. Two phylogenetic trees constructed from the substitutions at the synonymous site and the third codon position showed that the H1 hemagglutinin genes can be divided into three host-specific lineages. Examination of 21 hemagglutinin genes from the human and swine viruses revealed that two distinct lineages are present in the swine population. The swine strains, sw/North Ireland/38 and sw/Cambridge/39, are clearly on the human lineage, suggesting that they originate from a human A/WSN/33-like variant. However, the classic swine strain, sw/Iowa/15/30, and the contemporary human viruses are not direct descendants of the 1918 human pandemic strain, but did diverge from a common ancestral virus around 1905. Furthermore, previous to this the above mammalian viruses diverged from the lineage containing the avian viruses at about 1880.

Amino Acid Sequence↗

Potential for transmission of avian influenza viruses to pigs.

Pandemic strains of influenza A virus arise by genetic reassortment between avian and human viruses. Pigs have been suggested to generate such reassortants as intermediate hosts. In order for pigs to serve as 'mixing vessels' in genetic reassortment events, they must be susceptible to both human and avian influenza viruses. The ability of avian influenza viruses to replicate in pigs, however, has not been examined comprehensively. In this study, we assessed the growth potential of 42 strains of influenza virus in pigs. Of these, 38 were avian strains, including 27 with non-human-type haemagglutinins (HA; H4 to H13). At least one strain of each HA subtype replicated in the respiratory tract of pigs for 5 to 7 days to a level equivalent to that of swine and human viruses. These results indicate that avian influenza viruses with or without non-human-type HAs can be transmitted to pigs, thus raising the possibility of introduction of their genes into humans. Sera from pigs infected with avian viruses showed high titres of antibodies in ELISA and neutralization tests, but did not inhibit haemagglutination of homologous viruses, cautioning against the use of haemagglutination-inhibition tests to identify pigs infected with avian influenza viruses. Co-infection of pigs with a swine virus and with an avian virus unable to replicate in this animal generated reassortant viruses, whose polymerase and HA genes were entirely of avian origin, that could be passaged in pigs. This finding indicates that even avian viruses that do not replicate in pigs can contribute genes in the generation of reassortants.

Animals↗