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"Hang Le Khanh Nguyen"
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Tiger deaths in Vietnam due to infection with H5N1 highly pathogenic avian influenza virus bearing mutations associated with mammalian host adaptation
2025
Recently, infections with the H5N1 subtype of highly pathogenic avian influenza virus (H5N1-HPAIV) in mammals have been reported worldwide, including in cows in the United States and successive human cases in Cambodia. In Vietnam, 47 tigers and three leopards died from H5N1-HPAIV infection between August and October 2024. This study aimed to determine the origin of the H5N1 strains that infect tigers in Vietnam and to identify specific mutations associated with mammalian infection. Specimens were collected from tigers that died of suspected H5N1-HPAIV infection in southern Vietnam in September-October 2024. RNA was extracted and subjected to whole-genome sequencing. Time-stamped phylogenetic analysis was performed using H5N1 sequences recently detected in Vietnam and neighbouring countries. Phylogenetic results revealed that the strain found in tigers (Tiger H5N1 strain) belonged to clade 2.3.2.1e and was genetically close to the H5N1-HPAIV lineage responsible for ongoing human infections in Cambodia since 2023. Tiger H5N1 strains harboured several amino acid substitutions associated with mammalian host adaptation or transmissibility, such as E627 K in polymerase basic protein 2, similar to the Cambodian human H5N1 strains. This mammalian-adapted H5N1 lineage should be continuously monitored in poultry and mammals, including humans, in Vietnam to prevent further transmission.Recently, infections with the H5N1 subtype of highly pathogenic avian influenza virus (H5N1-HPAIV) in mammals have been reported worldwide, including in cows in the United States and successive human cases in Cambodia. In Vietnam, 47 tigers and three leopards died from H5N1-HPAIV infection between August and October 2024. This study aimed to determine the origin of the H5N1 strains that infect tigers in Vietnam and to identify specific mutations associated with mammalian infection. Specimens were collected from tigers that died of suspected H5N1-HPAIV infection in southern Vietnam in September-October 2024. RNA was extracted and subjected to whole-genome sequencing. Time-stamped phylogenetic analysis was performed using H5N1 sequences recently detected in Vietnam and neighbouring countries. Phylogenetic results revealed that the strain found in tigers (Tiger H5N1 strain) belonged to clade 2.3.2.1e and was genetically close to the H5N1-HPAIV lineage responsible for ongoing human infections in Cambodia since 2023. Tiger H5N1 strains harboured several amino acid substitutions associated with mammalian host adaptation or transmissibility, such as E627 K in polymerase basic protein 2, similar to the Cambodian human H5N1 strains. This mammalian-adapted H5N1 lineage should be continuously monitored in poultry and mammals, including humans, in Vietnam to prevent further transmission.
Journal Article
Novel Mutation of SARS-CoV-2, Vietnam, July 2020
by
Nhan, Nguyen thi Thanh
,
Nghia, Ngu Duy
,
Son, Nguyen Vu
in
2019 novel coronavirus disease
,
Bioinformatics
,
Caregivers
2021
A cluster of severe acute respiratory syndrome coronavirus 2 infections in Danang, Vietnam, began July 25, 2020, and resulted in 551 confirmed cases and 35 deaths as of February 2021. We analyzed 26 sequences from this cluster and identified a novel shared mutation in nonstructural protein 9, suggesting a single introduction into Vietnam.
Journal Article
Multiple polymerase gene mutations for human adaptation occurring in Asian H5N1 influenza virus clinical isolates
2018
The role of the influenza virus polymerase complex in host range restriction has been well-studied and several host range determinants, such as the polymerase PB2-E627K and PB2-D701N mutations, have been identified. However, there may be additional, currently unknown, human adaptation polymerase mutations. Here, we used a database search of influenza virus H5N1 clade 1.1, clade 2.3.2.1 and clade 2.3.4 strains isolated from 2008–2012 in Southern China, Vietnam and Cambodia to identify polymerase adaptation mutations that had been selected in infected patients. Several of these mutations acted either alone or together to increase viral polymerase activity in human airway cells to levels similar to the PB2-D701N and PB2-E627K single mutations and to increase progeny virus yields in infected mouse lungs to levels similar to the PB2-D701N single mutation. In particular, specific mutations acted synergistically with the PB2-D701N mutation and showed synergistic effects on viral replication both in human airway cells and mice compared with the corresponding single mutations. Thus, H5N1 viruses in infected patients were able to acquire multiple polymerase mutations that acted cooperatively for human adaptation. Our findings give new insight into the human adaptation of AI viruses and help in avian influenza virus risk assessment.
Journal Article
Highly Pathogenic Avian Influenza A(H5N1) Viruses at the Animal–Human Interface in Vietnam, 2003–2010
by
Tho, Nguyen Dang
,
Hoa, Do Ngoc
,
Thach, Nguyen Co
in
Amino Acid Sequence
,
Animals
,
Drug Resistance, Multiple, Viral
2017
Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal–human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance.
Journal Article
The 2017 Dengue virus 1 outbreak in northern Vietnam was caused by a locally circulating virus group
by
Takemura, Taichiro
,
Nguyen, Co Thach
,
Le, Thi Quynh Mai
in
Dengue virus
,
Infectious Diseases
,
Medicine
2022
Background
Dengue virus (DENV) is a member of insect vector-borne viruses, and it causes dengue fever. Southeast Asia is the epi-center of dengue fever in the world. The characterization of the virus is essential to identify the transmission and evolution of DENV.
Objectives
In 2017, there was an outbreak of Dengue virus type 1 (DENV1) in northern Vietnam and the neighboring countries. To identify the genetic character of the outbreak virus in the area, we conducted whole-genome sequencing analysis on the samples positive for the DENV1 along with real-time PCR.
Study design
In total, 1026 blood samples were collected from patients with suspected dengue fever in Ha Nam and Hai Duong province, nearby areas of the capital of Vietnam. After screening by real-time PCR, 40 of DENV1 positive samples were subjected to whole-genome sequencing, and 28 complete coding sequences were obtained.
Results
All 28 sequences were genotype I of DENV1, which is dominant in the southeast and East Asian countries. The phylogenetic analysis of the E region showed that they fell into a single cluster with the reported sequences from Vietnam between 2009 and 2016, in which the isolates from other countries are very rare. Our results suggested that the 2017 outbreak in the area was caused by locally circulating viruses.
Journal Article
Severe Acute Respiratory Syndrome Coronavirus 2 Shedding by Travelers, Vietnam, 2020
by
Takemura, Taichiro
,
Le, Thi Quynh Mai
,
Ngu, Duy Nghia
in
2019 novel coronavirus disease
,
Adolescent
,
Adult
2020
We analyzed 2 clusters of 12 patients in Vietnam with severe acute respiratory syndrome coronavirus 2 infection during January-February 2020. Analysis indicated virus transmission from a traveler from China. One asymptomatic patient demonstrated virus shedding, indicating potential virus transmission in the absence of clinical signs and symptoms.
Journal Article
Preclinical Immune Response and Safety Evaluation of the Protein Subunit Vaccine Nanocovax for COVID-19
2021
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern. The development of vaccines with high immunogenicity and safety is crucial for controlling the global COVID-19 pandemic and preventing further illness and fatalities. Here, we report the development of a SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the spike (S) protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG and neutralizing antibodies in three animal models: BALB/c mouse, Syrian hamster, and a non-human primate ( Macaca leonina ). In addition, a viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. Nanocovax did not induce any adverse effects in mice ( Mus musculus var. albino) and rats ( Rattus norvegicus ). These preclinical results indicate that Nanocovax is safe and effective.
Journal Article
Plans for Nationwide Serosurveillance Network in Vietnam
by
Nghia, Ngu Duy
,
Ha, Hoang Thi Thu
,
Pebody, Richard
in
Antibodies
,
Blood & organ donations
,
Collections
2020
In recent years, serosurveillance has gained momentum as a way of determining disease transmission and immunity in populations, particularly with respect to vaccine-preventable diseases. At the end of 2017, the Oxford University Clinical Research Unit and the National Institute of Hygiene and Epidemiology held a meeting in Vietnam with national policy makers, researchers, and international experts to discuss current seroepidemiologic projects in Vietnam and future needs and plans for nationwide serosurveillance. This report summarizes the meeting and the plans that were discussed to set up nationwide serosurveillance in Vietnam.
Journal Article
Discrepancies in Infectivity of Flavivirus and SARS-CoV-2 Clinical Samples: An Improved Assay for Infectious Virus Shedding and Viremia Assessment
by
Nguyen, Co Thach
,
Takemura, Taichiro
,
Le, Thi Quynh Mai
in
Cell culture
,
Dengue fever
,
Immunoglobulins
2021
Infectivity and neutralizing antibody titers of flavivirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are frequently measured using the conventional plaque assay. While the assay is useful in the determination of infectivity, conventional plaque assays generally possess lower sensitivity and are time-consuming compared to nucleic acid amplification tests. In this study, a microcrystalline cellulose (MCC), Avicel, was evaluated as an alternative to the conventional virus overlay medium, methylcellulose, for a plaque assay. The plaque assay was performed using dengue and COVID-19 clinical samples and laboratory-established flavivirus and SARS-CoV-2 strains. In virus titration of clinical samples, the plaques were significantly larger, and the virus titers were higher when Avicel MCC-containing overlay medium was used than with conventional methylcellulose overlay medium. In addition, for some clinical samples and laboratory virus strains, infectious particles were detected as plaques in the Avicel MCC-containing medium, but not in the conventional methylcellulose medium. The results suggest that the viremia titer determined using the new overlay medium containing Avicel MCC may better reflect the innate infectious and plaque-forming capabilities of clinical samples and better reflect virus infectivity.
Journal Article
Continued Circulation of Highly Pathogenic H5 Influenza Viruses in Vietnamese Live Bird Markets in 2018–2021
2023
We isolated 77 highly pathogenic avian influenza viruses during routine surveillance in live poultry markets in northern provinces of Vietnam from 2018 to 2021. These viruses are of the H5N6 subtype and belong to HA clades 2.3.4.4g and 2.3.4.4h. Interestingly, we did not detect viruses of clade 2.3.4.4b, which in recent years have dominated in different parts of the world. The viruses isolated in this current study do not encode major determinants of mammalian adaptation (e.g., PB2-E627K or PB1-D701N) but possess amino acid substitutions that may affect viral receptor-binding, replication, or the responses to human antiviral factors. Several of the highly pathogenic H5N6 virus samples contained other influenza viruses, providing an opportunity for reassortment. Collectively, our study demonstrates that the highly pathogenic H5 viruses circulating in Vietnam in 2018–2021 were different from those in other parts of the world, and that the Vietnamese H5 viruses continue to evolve through mutations and reassortment.
Journal Article