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Biomedical subjects

K F Shortridge

Publications and source records attributed to K F Shortridge.

At least 73 records · Page 4Linked to original sources
PubMed1992

Pandemic influenza: a zoonosis?

In the last two decades, influenza A viruses have been found to occur throughout the animal kingdom, mainly in birds, notably aquatic ones, in which infection is largely intestinal, waterborne, and asymptomatic. The domestic duck of southern China, raised in countless numbers all year round mainly as an adjunct to rice farming, is the principal host of influenza A viruses. Studies based on Hong Kong H3N2 viruses from southern China suggest that pandemic strains originate from the domestic duck there and are transmitted to humans via the domestic pig, which acts as a "mixing vessel" for two-way transmission of viruses. This provides further support for the hypothesis that the region is a hypothetical influenza epicenter. Rural dwellers in the epicenter show serological evidence of contact with non-human influenza A viruses. Two hypotheses are advanced for the range of hemagglutinin (HA) subtypes of viruses that can cause pandemics (1) circle or cycle limited to H1, H2, and H3 subtypes, thereby implying that a virus of the H2 subtype will cause the next pandemic; and (2) spiral, by which any one of the 14 HA subtypes recorded to date may be involved. Consideration is given to the temporal and geographical factors and range of hosts, namely the duck, pig, and human, that need to be submitted to virus surveillance in China and beyond to attempt to anticipate a future pandemic. Evidence is presented that points strongly to pandemic influenza being a zoonosis.

Animals↗
PubMed1991

Molecular evidence for a role of domestic ducks in the introduction of avian H3 influenza viruses to pigs in southern China, where the A/Hong Kong/68 (H3N2) strain emerged.

The haemagglutinins (HAs) of five H3 influenza A viruses isolated from domestic ducks and one from a goose in southern China were analysed antigenically and genetically. The patterns of reactivity of two of the duck viruses and the goose virus with a panel of monoclonal antibodies to 10 different epitopes on the H3 HA were similar to those of influenza viruses isolated from wild ducks and pigs, as well as those of the earliest human H3 viruses. The other three isolates from domestic ducks were different from each other and from these viruses antigenically. Sequence analysis revealed that the HA genes of the two duck viruses and the goose virus were closely related to those of isolates from wild ducks and pigs; the identities between the deduced amino acid sequence of the HA of one of the isolates from domestic ducks and those of isolates from a wild duck and a pig were 98.7% and 99.5%, respectively. The antigenic and genetic similarity between these H3 HAs suggests that in southern China, the hypothetical influenza epicentre, domestic ducks may have played a role in the introduction of avian influenza viruses to pigs from feral ducks. The findings also support the hypothesis that the pig was a 'mixing vessel', producing a new human pandemic strain, A/Hong Kong/68 (H3N2), by genetic reassortment.

Amino Acid Sequence↗
PubMed1990

Antigenic stability of H3 influenza viruses in the domestic duck population of southern China.

An antigenic analysis was carried out on 145 duck influenza virus isolates of the H3 haemagglutinin subtype obtained over five years continuous surveillance from the region of southern China, a hypothetical influenza epicentre. This was done using a panel of twelve monoclonal antibodies raised to an early human strain of the H3 subtype. We demonstrate the existence of an extensive range of antigenic profiles, broadly similar but not identical to the human H3 strain, which persisted over the five year period. This variability was as great during discrete twelve month periods as over the whole five years. Hierarchic progression (observed with human strains) was not evident and no correlation of antigenic drift, in either positive or negative direction, was observed with the domestic duck isolates over time. Changing dominant antigenic profiles were, however, observed in faecal isolates with time within a single farm. The much broader range of profiles detected in pond water samples from the same farm suggested the existence of a heterogeneous antigenic reservoir. Local switching of dominant profiles may occur due to changes of cohorts as birds are taken to market. In vitro and in vivo passage experiments revealed a high degree of heterogeneity in antigenic profiles in progeny of uncloned isolates, whereas the profiles of cloned isolates were largely conserved. These results suggested that particular antigenic profiles in primary isolates may result from mixtures of subpopulations of the wild type virus in natural duck infections. Switching between reactivity profiles of different progeny is likely to be largely a result of regrouping of these subpopulations with lesser effects due to mutation. Hypervariability in some of the cloned isolates was observed with a few monoclonal antibodies recognising a region of HA reported to be hypervariable in swine influenza virus. Reactivity with one particular antibody was correlated with passage in chicken eggs. The ability of this enormously varied pool of duck influenza H3 strains to cross the species barrier to man and give rise to viruses with hierarchic capabilities was considered.

Animals↗
PubMed1988

Origin of the hemagglutinin gene of H3N2 influenza viruses from pigs in China.

Influenza viruses of the H3N2 subtype similar to Aichi/2/68 and Victoria/3/75 persist in pigs many years after their antigenic counterparts have disappeared from humans (Shortridge et al. (1977). Science 19, 1454-1455). To provide information on the mechanism of conservation of these influenza viruses in pigs, the hemagglutinin (HA) of four isolates from swine derived from Taiwan and Southern China were analyzed antigenically and genetically. The reactivity pattern of these viruses with a panel of monoclonal antibodies indicates that the HAs of these swine viruses were antigenically closely related to duck H3 and early human H3 viruses. Sequence analysis of the H3 genes from three swine viruses revealed that the swine H3 genes are more closely related to the duck genes than to early human H3 virus (A/Aichi/2/68). The degree of sequence homology of these genes is extremely high (more than 96.5%). Furthermore, the deduced amino acid sequence of the three swine HAs at residues 226 to 228 in the proposed receptor-binding site is Gln-Ser-Gly and is common with the majority of avian influenza viruses. These findings indicate that these H3 viruses may have been introduced into pigs from ducks. The HA gene of the fourth swine influenza virus from Southern China was genetically equally related to avian and early human H3 strains although the sequence through the receptor-binding pocket (226-228) was typical of a human H3 virus, suggesting that either this swine HA gene was derived from ducks or an early human H3 virus was introduced into the pig population where the virus accumulated substantial mutations. The present strains revealed genetic heterogeneity of swine H3 influenza viruses in nature.

Amino Acid Sequence↗
PubMed1987

Newcastle disease vaccine (La Sota) strain specific monoclonal antibody. Brief report.

Newcastle disease virus vaccine strain (La Sota) specific monoclonal antibody (La-1) was produced by immunizing mice with isolated glycoproteins of strain La Sota. This antibody was recognized only in the ELISA test in which it bound exclusively to La Sota strain out of a range of over 300 lentogenic, mesogenic and velogenic strains examined.

Animals↗
PubMed1987

Serological evidence of Hantaan-related viruses in Hong Kong.

Sera from rats (Rattus norvegicus), domestic animals and man in Hong Kong were studied by immunofluorescent antibody assay and plaque reduction neutralization tests for evidence of infection by Hantaan-related viruses. Antibody probably arising from infection by Seoul or a Seoul-like virus was detected in rat and human sera (and one pig serum), highlighting the potential public health importance of this group of viruses in Hong Kong, and in the region.

Adolescent↗
PubMed1987

Bile immunoglobulin of the duck (Anas platyrhynchos). II. Antibody response in influenza A virus infections.

The capacity of the IgM-like bile immunoglobulin (IgX) of the duck (Anas platyrhynchos) to express antibody activity to H3N2 influenza A viruses, and the dependence of this activity on the co-existence of serum IgM antibodies were investigated. Ducklings infected orally and intranasally at 15-29 days of age with viruses isolated from different host species were examined for haemagglutination-inhibiting (HI) antibodies in biles and sera 16-29 days after infection (p.i.). All biles had antibodies associated with IgX; all sera had antibodies associated only with the 7.8S IgG. Following oral infection of birds 42-days-old with influenza A/duck/HK/7/75 virus, serum HI antibodies were an initial IgM response occurring from 5-12 days p.i., followed by the appearance of 7.8S IgG antibodies. Virus-neutralizing (VN) antibodies in serum were also biphasic; isotype classification was not attempted. Bile IgX developed HI and VN activity. HI antibodies reached peak titres 12 days p.i. and fell to low levels by 24 days p.i. VN antibodies also reached peak titres 12 days p.i., but thereafter persisted at quite high levels throughout the experiment. Development of high titres of antibody in bile coincided with the termination of virus excretion in faeces. These experiments confirm that bile IgX of the duck can function as antibody in response to influenza A viruses, and that its activity appears to be independent of serum IgM. Its possible relevance in determining survival of virus in the intestine is discussed.

Animals↗
PubMed1986

Global survey of antibody to Hantaan-related viruses among peridomestic rodents.

A global serological survey of rodents was conducted to determine the distribution and prevalence of antibody to Hantaan-related viruses, which are the causative agents of haemorrhagic fever with renal syndrome (HFRS) in man. Over 1700 rodent sera from more than 20 sites worldwide were examined by immunofluorescent antibody assay. High-titred positive sera were further tested by plaque reduction neutralization tests with prototype Hantaan virus and urban rat-associated Hantaan-like virus. Antibody-positive rodents were found in most, but not all, sites sampled. The highest antibody prevalence rates were found in Baltimore, MD, USA and Bélem, Brazil, and Rattus norvegicus was the species most often found positive. Bandicota indica and B. bengalensis, species previously not recognized as hosts of hantaviruses, were also positive. Neutralization tests detected antibody in Rattus sera specific for urban rat-associated Hantaan-like virus, but failed to establish the specificity of antibody in Bandicota sera. These results indicate that Hantaan-related viruses exist beyond the currently recognized boundaries of HFRS in man and suggest that human HFRS-like disease might be occurring in other areas of the world where rodent-human contact is common.

Africa↗
PubMed1985

The nucleoprotein as a possible major factor in determining host specificity of influenza H3N2 viruses.

In an attempt to assess the importance of the nucleoprotein (NP) in the determination of host specificity, a series of experiments was performed on influenza A viruses of the H3N2 subtype. We have examined rescue of mutants of A/FPV/Rostock/34 with temperature-sensitive (ts) lesions in the nucleoprotein (NP) gene by double infection of chick embryo cells with H3N2 strains isolated from different species. The ts mutants could be rescued by all avian H3N2 strains but not by any of the human H3N2 isolates. Only two of the swine H3N2 strains tested were able to rescue our mutants. The NP gene of these two swine isolates resembled the NP gene of the avian strains genetically in the hybridization test. However, their NPs reacted differently with a set of monoclonal antibodies when compared with NPs of avian H3N2 strains. Concerning multiplication in ducks they behaved like the other swine and human strains. The phosphopeptide fingerprints of all swine isolates tested were alike and were different from those of human or avian origin. Our observations are compatible with the idea that human H3N2 strains might not be able to cross the species barrier to birds directly, and possibly also not the other way around, without prior reassortment in pigs, which seem to have a broader host range concerning the compatibility of the NP gene in reassortants.

Animals↗
PubMed1983

Cocultivation of avian orthomyxoviruses and paramyxoviruses in embryonated eggs: implications for surveillance studies.

A series of avian orthomyxoviruses and paramyxoviruses were cocultivated in embryonated chicken eggs. This resulted in two categories of behavior being observed: (i) one virus was preferentially detected over the other, as shown by five out of six influenza A viruses of differing hemagglutinin subtypes being preferentially detected over paramyxoviruses, and (ii) dual isolations, for example, dual isolations of paramyxoviruses. These findings are considered in the light of results of surveillance studies of orthomyxoviruses and paramyxoviruses carried out on domestic poultry in Hong Kong.

Animals↗
PubMed1982

Possible waterborne transmission and maintenance of influenza viruses in domestic ducks.

Two duck farms in Hong Kong were examined monthly for 1 year for the occurrence and persistence of influenza viruses within the duck communities. The predominant virus in one community was H3N2, a virus antigenically related to the pandemic Hong Kong strain. This virus was isolated monthly throughout the year from feces or pond water or both, indicating a cycle of waterborne transmission. Viruses of the same antigenic combination were isolated 1 and 2 years after the last sampling occasion, implying persistence in the community. Infection was asymptomatic. Maintenance of virus appeared to be dependent upon the continual introduction of ducklings susceptible to infection onto virus-contaminated water; the feces of ducks 70 to 80 days old were generally free of detectable virus despite the exposure of the ducks to virus in pond water. In the second community, in which ducklings were not introduced after the initial sampling, the prevailing viruses, H7N1 and H7N2, also present asymptomatically, ceased to be detected once the ducks were 70 to 80 days old. The normal practice of raising ducks of different ages on the same farm, wherein the water supplies are shared, as typified by the first community, appears to be instrumental in maintaining a large reservoir of influenza viruses in the duck population of southern China.

Animals↗