Molecular and Serological Epidemiology Studies on Interspecies Transmitted Human Influenza Viruses in Taiwan Area
Date Issued
2004
Date
2004
Author(s)
Liao, Yi-Jen
DOI
zh-TW
Abstract
The emergence of novel influenza viruses poses a pandemic public health threat. Since 1997, new avian influenza A viruses such as H5N1, H9N2 and H7N7 influenza viruses emerged in Hong Kong, China, Netherlands and Hong Kong, China, Vietnam and Thailand, resulting in human fatal cases and most of these cases had contact histories of avian. Seroepidemiological studies reveal that poultry workers and health care workers are the high-risk populations. Since Taiwan and Kinmen have high densities of swine/domestic avian farms, habitats of migrating birds and tremendous numbers of travelers going to mainland China and Hong Kong, integrated human influenza virological surveillance systems had been established in six areas (Taipei, Yilan, Taoyuan, Changhua, Tainan, Pingting County and Kinmen islet) from Dec. 2002 to Mar. 2004. The specific aims of this study are: (1) to investigate the potential avian-to-human transmission by evaluating molecular changes in human influenza A viruses in those high risk populations who live near the poultry or farms with animal flu epidemics or novel influenza viruses isolated (H1N2, H3N1, H5 and H7), and who have contacts with swine or avian or travel histories to China/Hong Kong before the onset of illness, (2) to evaluate their serological responses to H5, H6 and H7 avian influenza viruses, and (3) to monitor micro-evolutionary changes of those human influenza isolates obtained from Taiwan main island versus Kinmen islet.
All of 31 influenza A viruses in total isolated from two flu seasons from Dec. 2002 to Mar. 2004 were A/Fujian/411/02-like (H3N2) by phylogenetic and amino acid analysis of HA gene and the sialic receptor binding sites of HA did not have any avian flu specific amino acid signatures either. All other 7 genes also belong to the lineage of human influenza viruses. Three patients, including: (l) ID#618 lived near the chicken farm and her parents are poultry workers, (2) ID#712 lived close to the chicken, pig and pigeon farms, and (3) ID#704 raised birds and lived near the chicken farms, had specific mutation sites at Asn31Asp, Ser45Asn and Gly479Glu in the HA1, respectively and their amino acids at these three sites were similar to avian and swine flu H3 viruses. In NA gene, Arg210Met, which was found in one patient ID#639 who had contact with pigs before illness, was also identical to avian N2 subtype. No such relationships in amino acids between human flu isolates and animal flu viruses were observed among the rest of 6 internal genes.
In comparing human influenza isolates obtained between two flu seasons, 9 amino acids substitution in HA and NA genes were found significantly different, including: (1) two sites near the antibody combining sites of HA [Gln156His (7/13 vs. 17/17, p=0.0009) and Ser193Asn (1/13 vs. 9/17, p=0.048)], (2) another two sits of HA [Ser189Asn (0/13 vs. 4/17, p=0.027) and Asn547Asp (0/10 vs. 6/13, p=0.006)], (3) one of the antibody epitopes of NA [Glu199Lys (0/9 vs. 6/17, p=0.025)], (4) other 3 mutated residues of NA [Val216Gly, Thr265Ile and Ile307Val (0/11 vs. 4/17, p=0.049)], and (5) Ser227Pro in HA gene was initially observed only in Kinmen isolates in 2002~2003 flu season, but such a Pro then became as a dominant amino acid in Taiwan’s 2003~2004 flu isolates. Additionally, three mutated amino acids in HA1, including Leu157Ser, Tyr159Phe and Val309Ile, which were found in 2/3 Kinmen isolates during 2003~2004 (0/12 vs. 2/3, p=0.01), can be served as a basis to monitor possible changes of 2005’s flu isolates in Taiwan island.
Seroepidemiological study on 219 high risk populations, including 59 animal health research institute workers, 90 poultry workers, 46 swine workers, and 24 elderly in Kinmen found that all of them were seronegative against three subtypes of Taiwan’s avian flu viruses [A/Duck/Taipei/A30/02 (H5N2), A/Duck/Tainan/A45/03 (H7N7) and A/Chicken/Taiwan/3153/04 (H6N1)] by micro-neutralization test.
In conclusion, our molecular and serological epidemiology studies have not had any evidences to support avian to human transmission of novel influenza viruses in Taiwan area. Furthermore, human influenza viruses H3N2 had temporal changes in HA and NA genes between two seasons and spatial differences in Taiwan vs. Kinmen. Four flu patients living near animal farms showed specific amino acid signatures of HA and NA identical to animal influenza A viruses. Future efforts will monitor the microevolution and macroevolution of influenza viruses in human, avian and swine obtained in the same and different areas over years for better understandings in the mechanisms that emerging novel human flu viruses might have public health significance.
Subjects
跨越宿主傳播
分子與血清流行病學偵測
A型流行性感冒病毒
Molecular and Serological Surveillance
Interspecies Transmission
Influenza A Viruses
SDGs
Type
thesis
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