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J S M Peiris

Publications and source records attributed to J S M Peiris.

At least 19 recordsLinked to original sources
PubMed2007

Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.

Poor human-to-human transmission of influenza A H5N1 virus has been attributed to the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of the human upper respiratory tract, and thus to the presumed inability of the virus to replicate efficiently at this site. We now demonstrate that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.

Cells, Cultured↗
PubMed2006

Comparative analytical sensitivities of six rapid influenza A antigen detection test kits for detection of influenza A subtypes H1N1, H3N2 and H5N1.

BACKGROUND: Rapid and simple methods for diagnosing human influenza A (H5N1) disease urgently needed. The limited data so far suggest that the currently available rapid antigen detection kits have poor clinical sensitivity for diagnosis of human H5N1 disease. OBJECTIVES: To compare the analytical sensitivity of six commercially available rapid antigen detection kits for the detection of "human" (subtypes H1N1, H3N2) and "avian" (subtype H5N1) influenza A viruses. STUDY DESIGN: Six commercially available test kits for the detection of influenza A were investigated. Analytic sensitivity for the detection of two contemporary H1N1, two H3N2 and three H5N1 viruses was determined using virus culture as a reference method. RESULTS AND CONCLUSIONS: Each test kit detected the H5N1 virus subtypes as efficiently as they detected conventional human viruses of subtypes H1N1 or H3N2. However, limits of detection of influenza viruses of all subtypes by antigen detection kits were >1000-fold lower than virus isolation. Thus, the reportedly poor clinical sensitivity of these antigen detection kits for diagnosis of patients with H5N1 disease is not due to a difference of sensitivity for detecting avian influenza H5N1 compared to human influenza viruses.

Animals↗
PubMed2006

Evolution and molecular epidemiology of H9N2 influenza A viruses from quail in southern China, 2000 to 2005.

H9N2 influenza viruses have become established and maintain long-term endemicity in terrestrial poultry in Asian countries. Occasionally these viruses transmit to other mammals, including humans. Increasing epidemiological and laboratory findings suggest that quail may be an important host, as they are susceptible to different subtypes of influenza viruses. To better understand the role of quail in influenza virus ecology and evolution, H9N2 viruses isolated from quail during 2000 to 2005 were antigenically and genetically characterized. Our results showed that H9N2 viruses are prevalent year-round in southern China and replicate mainly asymptomatically in the respiratory tract of quail. Genetic analysis revealed that both the G1-like and Ck/Bei-like H9N2 lineages were cocirculating in quail since 2000. Phylogenetic analyses demonstrated that most of the isolates tested were double- or multiple-reassortant variants, with four G1-like and 16 Ck/Bei-like genotypes recognized. A novel genotype of G1-like virus became predominant in quail since 2003, while multiple Ck/Bei-like genotypes were introduced into quail, wherein they incorporated G1-like gene segments, but none of them became established in this host. Those Ck/Bei-like reassortants generated in quail have then been introduced into other poultry. These complex interactions form a two-way transmission system between quail and other types of poultry. The present study provides evidence that H9N2 and H5N1 subtype viruses have also exchanged gene segments to generate currently circulating reassortants of both subtypes that have pandemic potential. Continuing influenza virus surveillance in poultry is critical to understanding the genesis and emergence of potentially pandemic strains in this region.

Amino Acid Motifs↗
PubMed2006

Emergence and predominance of an H5N1 influenza variant in China.

The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.

Animals↗
PubMed2006

Avian influenza H5N1 in viverrids: implications for wildlife health and conservation.

The Asian countries chronically infected with avian influenza A H5N1 are 'global hotspots' for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range.

Animals↗
PubMed2006

Evolution and adaptation of H5N1 influenza virus in avian and human hosts in Indonesia and Vietnam.

Highly pathogenic avian influenza virus H5N1 is endemic in poultry in East and Southeast Asia with disease outbreaks recently spreading to parts of central Asia, Europe and Africa. Continued interspecies transmission to humans has been reported in Vietnam, Thailand, Cambodia, Indonesia and China, causing pandemic concern. Here, we genetically characterize 82 H5N1 viruses isolated from poultry throughout Indonesia and Vietnam and 11 human isolates from southern Vietnam together with sequence data available in public databases to address questions relevant to virus introduction, endemicity and evolution. Phylogenetic analysis shows that all viruses from Indonesia form a distinct sublineage of H5N1 genotype Z viruses suggesting this outbreak likely originated from a single introduction that spread throughout the country during the past two years. Continued virus activities in Indonesia were attributed to transmission via poultry movement within the country rather than through repeated introductions by bird migration. Within Indonesia and Vietnam, H5N1 viruses have evolved over time into geographically distinct groups within each country. Molecular analysis of the H5N1 genotype Z genome shows that only the M2 and PB1-F2 genes were under positive selection, suggesting that these genes might be involved in adaptation of this virus to new hosts following interspecies transmission. At the amino acid level 12 residues were under positive selection in those genotype Z viruses, in the HA and PB1-F2 proteins. Some of these residues were more frequently observed in human isolates than in avian isolates and are related to viral antigenicity and receptor binding. Our study provides insight into the ongoing evolution of H5N1 influenza viruses that are transmitting in diverse avian species and at the interface between avian and human hosts.

Animals↗
PubMed2006

Immune response to influenza vaccination in community-dwelling Chinese elderly persons.

We investigated the immune antibody response to influenza vaccine in community-dwelling Chinese elderly persons in Hong Kong. One hundred and twenty-eight subjects were recruited in a single-blind, randomized, and placebo-controlled trial. There was no significant baseline difference between the vaccine and placebo groups regarding the seroprotection rates (PR) (haemagglutination inhibition [HI] titre>or=1:40) and geometric mean titres (GMT) of the HI antibody titers. The PR, GMTs and serological response rates increased significantly in the vaccinated versus placebo groups in A-H1N1 at both weeks 4 and month 6. The GMTs and serological response rates but not the PR for A-H3N2 and influenza B increased significantly in vaccinated versus placebo group at week 4 and month 6 post-vaccination. Multivariate logistic regression analyses of the seroconversion rate for A-H3N2 within the vaccinated group showed that gender, coronary heart disease and the serum albumin level were significant predictors (p=0.018, 0.009 and 0.025, respectively). Influenza vaccination provoked a protective HI antibody response in community-living Chinese elderly persons. The mean number of unplanned hospital admissions per subject over 6 months was significantly lower in the vaccinated than in the placebo groups. Hospitalized elderly persons had poorer nutrition, 4-week post-immunization HI antibody titres and lower mini-mental state examination (MMSE) score than non-hospitalized elderly persons. Logistic regression analyses showed that chronic obstructive airway disease significantly increased the risk of hospitalization while the serum albumin level and 4-week A-H3N2 PR (HI>or=40) were independent predictors of a decreased risk of hospitalizations.

Aged↗
PubMed2006

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control.

Preparedness for a possible influenza pandemic caused by highly pathogenic avian influenza A subtype H5N1 has become a global priority. The spread of the virus to Europe and continued human infection in Southeast Asia have heightened pandemic concern. It remains unknown from where the pandemic strain may emerge; current attention is directed at Vietnam, Thailand, and, more recently, Indonesia and China. Here, we report that genetically and antigenically distinct sublineages of H5N1 virus have become established in poultry in different geographical regions of Southeast Asia, indicating the long-term endemicity of the virus, and the isolation of H5N1 virus from apparently healthy migratory birds in southern China. Our data show that H5N1 influenza virus, has continued to spread from its established source in southern China to other regions through transport of poultry and bird migration. The identification of regionally distinct sublineages contributes to the understanding of the mechanism for the perpetuation and spread of H5N1, providing information that is directly relevant to control of the source of infection in poultry. It points to the necessity of surveillance that is geographically broader than previously supposed and that includes H5N1 viruses of greater genetic and antigenic diversity.

Animals↗
PubMed2006

Development of vaccines and passive immunotherapy against SARS coronavirus using mouse and SCID-PBL/hu mouse models.

We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD-SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The M DNA vaccine enhanced CTL activity and proliferation in the presence of M peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL activity (IFN-gamma production by recombinant N protein or N protein-pulsed autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice. These results, demonstrate that SARS M and N DNA vaccines induced human CTL and human T-cell proliferative responses. On the other hand, we have developed SARS DNA vaccines that induce human neutralizing antibodies and human monoclonal antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor (angiotensin converting enzyme 2) are also under development. These vaccines are expected to induce immune responses specific for SARS CoV in human and should provide useful tool for development of protective vaccines.

Animals↗
PubMed2006

Coronaviruses in bent-winged bats (Miniopterus spp.).

A novel group 1 coronavirus was previously identified in bent-winged bats (Miniopterus spp.). Here, results are described from our ongoing surveillance of these bats for coronaviruses. These findings show that group 1 coronaviruses are endemic in these bat populations in Hong Kong. Genetic analysis of these viruses indicates that there are at least four different, but closely related, group 1 coronaviruses (bat-CoV 1A, 1B, HKU7 and HKU8) circulating in bent-winged bats. Phylogenetic analysis revealed that these group 1 bat coronaviruses have descended from a common ancestor and that these viruses have been established in these bats for a long period of time. These data provide a better understanding of the emergence and evolution of coronaviruses. Bat-CoV 1A and 1B were detected in apparently healthy Miniopterus magnater and Miniopterus pusillus, respectively, on repeated sampling occasions at a single habitat, suggesting that these viruses have established a persistent infection in these populations.

Amino Acid Sequence↗
PubMed2006

Prevalence and genetic diversity of coronaviruses in bats from China.

Coronaviruses can infect a variety of animals including poultry, livestock, and humans and are currently classified into three groups. The interspecies transmissions of coronaviruses between different hosts form a complex ecosystem of which little is known. The outbreak of severe acute respiratory syndrome (SARS) and the recent identification of new coronaviruses have highlighted the necessity for further investigation of coronavirus ecology, in particular the role of bats and other wild animals. In this study, we sampled bat populations in 15 provinces of China and reveal that approximately 6.5% of the bats, from diverse species distributed throughout the region, harbor coronaviruses. Full genomes of four coronavirues from bats were sequenced and analyzed. Phylogenetic analyses of the spike, envelope, membrane, and nucleoprotein structural proteins and the two conserved replicase domains, putative RNA-dependent RNA polymerase and RNA helicase, revealed that bat coronaviruses cluster in three different groups: group 1, another group that includes all SARS and SARS-like coronaviruses (putative group 4), and an independent bat coronavirus group (putative group 5). Further genetic analyses showed that different species of bats maintain coronaviruses from different groups and that a single bat species from different geographic locations supports similar coronaviruses. Thus, the findings of this study suggest that bats may play an integral role in the ecology and evolution of coronaviruses.

Animals↗
PubMed2006

Use of avian influenza vaccination in Hong Kong.

Outbreaks of H5N1 highly pathogenic avian influenza (HPAI) that occurred in Hong Kong up until February/March 2002 were controlled by stamping out. With endemic presence of the virus in the region and large daily importation of poultry to Hong Kong, the Administration considered that further risk management measures, in addition to improved biosecurity and enhanced surveillance, were necessary to prevent outbreaks. Vaccination using a killed H5N2 vaccine was evaluated over a 12-month period in the district with the last HPAI cases in the early 2002 outbreak. The vaccination trial showed that farmer-administered killed H5N2 vaccine produced suitable flock antibody responses; vaccinated birds were protected against H5N1 HPAI virus challenge and excreted significantly less H5N1 virus; and vaccination was able to control virus excretion in flocks during field outbreaks. Universal vaccination of local chicken farms was introduced in June 2003 and by the end of 2003 all chickens entering the live poultry markets in Hong Kong were vaccinated by killed H5N2 vaccine. In addition to vaccination, an enhanced biosecurity programme on farms and in live poultry markets and a comprehensive surveillance programme in poultry, wild birds, recreation park birds and pet birds were in place. Vaccination use and performance is closely monitored. This programme was successful in protecting local farms and live poultry markets from H5N1 outbreaks during the regional H5N1 outbreaks in 2004.

Animals↗
PubMed2005

Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells.

BACKGROUND: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.

Bronchi↗
PubMed2005

Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia.

Wild waterfowl, including ducks, are natural hosts of influenza A viruses. These viruses rarely caused disease in ducks until 2002, when some H5N1 strains became highly pathogenic. Here we show that these H5N1 viruses are reverting to nonpathogenicity in ducks. Ducks experimentally infected with viruses isolated between 2003 and 2004 shed virus for an extended time (up to 17 days), during which variant viruses with low pathogenicity were selected. These results suggest that the duck has become the "Trojan horse" of Asian H5N1 influenza viruses. The ducks that are unaffected by infection with these viruses continue to circulate these viruses, presenting a pandemic threat.

Animals↗
PubMed2005

Human coronavirus NL63 infection and other coronavirus infections in children hospitalized with acute respiratory disease in Hong Kong, China.

BACKGROUND: Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). METHODS: We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. RESULTS: Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (+/- standard deviation [SD]) of the infected children was 30.7 +/- 19.8 months (range, 6-57 months). The mean maximum temperature (+/- SD) for the 12 children who were febrile was 39.3 degrees C +/- 0.9 degrees C, and the mean total duration of fever (+/- SD) for all children was 2.6 +/- 1.2 days (range, 1-5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. CONCLUSIONS: HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged < or = 6 years each year in Hong Kong.

Adolescent↗
PubMed2005

The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice.

We have investigated to develop novel vaccines against SARS CoV using cDNA constructs encoding the structural antigen; spike protein (S), membrane protein (M), envelope protein (E), or nucleocapsid (N) protein, derived from SARS CoV. Mice vaccinated with SARS-N or -M DNA using pcDNA 3.1(+) plasmid vector showed T cell immune responses (CTL induction and proliferation) against N or M protein, respectively. CTL responses were also detected to SARS DNA-transfected type II alveolar epithelial cells (T7 cell clone), which are thought to be initial target cells for SARS virus infection in human. To determine whether these DNA vaccines could induce T cell immune responses in humans as well as in mice, SCID-PBL/hu mice was immunized with these DNA vaccines. As expected, virus-specific CTL responses and T cell proliferation were induced from human T cells. SARS-N and SARS-M DNA vaccines and SCID-PBL/hu mouse model will be important in the development of protective vaccines.

Animals↗