Publications by authors named "Thi Quynh Mai Le"

11 Publications

  • Page 1 of 1

Macrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models.

Nat Commun 2021 May 11;12(1):2654. Epub 2021 May 11.

Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.

Most anti-influenza drugs currently used, such as oseltamivir and zanamivir, inhibit the enzymatic activity of neuraminidase. However, neuraminidase inhibitor-resistant viruses have already been identified from various influenza virus isolates. Here, we report the development of a class of macrocyclic peptides that bind the influenza viral envelope protein hemagglutinin, named iHA. Of 28 iHAs examined, iHA-24 and iHA-100 have inhibitory effects on the in vitro replication of a wide range of Group 1 influenza viruses. In particular, iHA-100 bifunctionally inhibits hemagglutinin-mediated adsorption and membrane fusion through binding to the stalk domain of hemagglutinin. Moreover, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models. This study shows the potential for developing cyclic peptides that can be produced more efficiently than antibodies and have multiple functions as next-generation, mid-sized biomolecules.
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http://dx.doi.org/10.1038/s41467-021-22964-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113231PMC
May 2021

Prevalence of Zika virus neutralizing antibodies in healthy adults in Vietnam during and after the Zika virus epidemic season: a longitudinal population-based survey.

BMC Infect Dis 2020 May 11;20(1):332. Epub 2020 May 11.

Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.

Background: Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant's family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region.

Methods: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive.

Results: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were confirmed to be ZIKV antibodies positive using PRNT and anti-ZIKV IgG ELISA. Of the 718 participants who were anti-ZIKV IgM negative, a further 3 cases were confirmed as positive for antibodies against ZIKV. Of the 9 participants with ZIKV infection, 5 lived in the same village as the infant with ZIKV-associated microcephaly and the other 4 lived in 2 neighboring communes. Repeat samples were collected from the 83 ZIKV IgM positive participants 1.5 years after the first collection. No new cases of ZIKV infection were detected. In addition, 2 of 3 participants with anti-ZIKV NS1 IgG demonstrated a 4- to 8-fold increase in ZIKV neutralizing antibody titer.

Conclusions: ZIKV was present in the area around Krong Buk, with the rate of ZIKV-specific antibodies was 1.1% in the community since at least 2016. While the low levels of circulation together with low seroprevalence suggests a limited outbreak in the region, the results also reflect on low levels of protective immunity to Zika within the population. These results provide a better understanding of the current ZIKV epidemic status in the region and demonstrate a need for implementation of more effective ZIKV infection control measures.
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http://dx.doi.org/10.1186/s12879-020-05042-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216417PMC
May 2020

Severe Acute Respiratory Syndrome Coronavirus 2 Shedding by Travelers, Vietnam, 2020.

Emerg Infect Dis 2020 07 21;26(7):1624-1626. Epub 2020 Jun 21.

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.
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http://dx.doi.org/10.3201/eid2607.200591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323563PMC
July 2020

Clinical, Virological, and Cytokine Profiles of Children Infected with Dengue Virus during the Outbreak in Southern Vietnam in 2017.

Am J Trop Med Hyg 2020 06;102(6):1217-1225

Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Dengue virus (DENV) infection is a major cause of morbidity and mortality in Vietnam, and the incidence is higher and more consistent in the southern part of the country. This study investigated the circulation of DENV serotypes, viremia levels, immunological status, and cytokine levels, with disease severities among children infected in 2017 in Ho Chi Minh City, Southern Vietnam. Acute and convalescent serum samples were collected from clinically diagnosed dengue children. They were confirmed to have DENV infection by NS1 antigen, IgM and IgG ELISAs, virus isolation, and conventional and real-time RT-PCR. Measurement of 10 cytokine levels was performed in the serum samples. All the children were dengue IgM positive; 28% and 72% of them had primary and secondary DENV infections, respectively, whereas 54% of those with secondary infection were children with dengue with warning signs and with severe dengue. Any or mixed infection of the four serotypes of DENV RNA was detected in 58 children. Twenty DENV strains (DENV-1 = 16 and DENV-4 = 4) were isolated. Levels of IFN-γ, TNF-α, MCP-1, IL-10, and IL-6 were significantly higher in severe dengue cases. We report the predominance of DENV-1 over other serotypes in the 2017 dengue outbreak in Southern Vietnam. Our data showed that cytokine expressions were correlated with dengue pathogenesis and may help in identifying an effective therapeutic strategy.
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http://dx.doi.org/10.4269/ajtmh.19-0607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253104PMC
June 2020

Long-term surveillance needed to detect Zika virus outbreaks in endemic regions.

Lancet Infect Dis 2020 02;20(2):168-169

WHO Collaborating Centre for Reference and Research on Tropical and Emerging Virus Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(19)30677-2DOI Listing
February 2020

Dengue virus infection-enhancement activity in neutralizing antibodies of healthy adults before dengue season as determined by using FcγR-expressing cells.

BMC Infect Dis 2018 01 10;18(1):31. Epub 2018 Jan 10.

Department of Virology, Institute of Tropical Medicine, Nagasaki University, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.

Background: Antibodies are critical responses to protect the host from dengue virus(DENV) infection. Antibodies target DENV by two pathologic mechanisms: virus neutralization and infection enhancement. In dengue patients, the absence of neutralizing activity in the presence of FcγR implies that infection-enhancing activity hampers the neutralizing activity of antibodies, which could potentially lead to symptomatic presentations and severe clinical outcomes.

Methods: A total of 100 pair serum samples from adult healthy volunteers were obtained during the dengue season in Ha Noi in 2015 for evaluation of neutralizing and infection-enhancing activity. Additionally, 20 serum samples from acute secondary DENV infection patients were also used as the patient group in this study. PRNT was performed on BHK cells and FcγR-expressing BHK cell lines for all serum samples.

Results: Out of 100 residents, positive neutralizing antibodies (N.A) were found in 44.23 and 76.92% for DENV-1; 38.46 and 75% for DENV-2; 19.23 and 15.38% for DENV-3; and 1.92 and 9.62% for DENV-4 for pre and post-dengue season respectively. The percentage of post-exposure residents having positive responses against single, two, or more than three DENV serotypes were 38.46, 44.23 and 15.38%, respectively. A total of 34 residents were DENV seropositive before the dengue season and these individuals demonstrated further elevation of IgG antibodies after the dengue season. At the end of the season, 18 residents were confirmed to be new asymptomatic DENV infection cases. In both groups, N.A titers determined on BHK cells were higher than that on FcγR-expressing BHK cells. In heterotypic N.A responses, N.A titers to the infecting serotype from the samples obtained from pre-exposure group were significantly higher than those of the patient group. However, fold enhancement to the infecting serotypes from the samples in the pre-exposure group was substantially lower as compared to that of the patient group.

Conclusion: Before and after the dengue season, serum samples from healthy volunteers demonstrated high levels of neutralizing antibodies and low or absence of infection-enhancement activity. The results suggest that while infection-enhancement activity hampers neutralizing activity of antibodies, high levels of DENV neutralizing antibodies set a critical threshold in facilitating the prevention of disease progression.
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http://dx.doi.org/10.1186/s12879-017-2894-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763606PMC
January 2018

Zika virus infection and microcephaly in Vietnam.

Lancet Infect Dis 2017 08;17(8):805-806

WHO Collaborating Centre for Reference and Research on Tropical and Emerging Virus Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(17)30412-7DOI Listing
August 2017

Dengue Associated Acute Encephalitis Syndrome Cases in Son La Province, Vietnam in 2014.

Jpn J Infect Dis 2017 07 31;70(4):357-361. Epub 2016 Oct 31.

Department of Virology, Institute of Tropical Medicine, Nagasaki University.

Acute encephalitis syndrome (AES) is associated with high morbidity and mortality, and affects both children and adults. The main etiologic agent is Japanese encephalitis virus (JEV); however, there are also reports of Dengue virus (DENV) encephalitis. The objectives of this study were to determine the proportion of patients with encephalitis due to JEV during the 2014 outbreak in Son La Province in Vietnam and to explore the association of DENV in non-JEV viral encephalitis cases. Of 90 patients, 6 (6.7%) were positive for anti-JEV immunoglobulin M (IgM), 5 (5.6%) were positive for anti-DENV IgM, 30 (33.3%) were positive for both anti-JEV and anti-DENV IgM, and 56 (62.2%) were positive for flavivirus immunoglobulin G (IgG). In 5 patients with AES, who had positive anti-DENV IgM results in at least one of the paired serum samples, DENV was confirmed by neutralization testing. The incidence of JEV infection was high. There is still a need to maintain and strengthen the national JEV immunization program. This noticeable occurrence of DENV infection was not reported in Son La Province in 2013-2014. Our data suggested that in addition to JEV, DENV was also a causative agent of AES in 2014 in Son La Province, and this finding also confirmed the local occurrence of DENV infection.
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http://dx.doi.org/10.7883/yoken.JJID.2016.246DOI Listing
July 2017

Pathogenicity of H5N1 influenza A viruses isolated in Vietnam between late 2003 and 2005.

J Vet Med Sci 2006 Jul;68(7):735-7

International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Since late 2003, highly pathogenic H5N1 influenza A viruses have spread among poultry and wild aquatic birds in Asian countries. Transmission of these viruses to humans can be lethal. Most human cases of infection with H5N1 viruses have occurred in Vietnam. Therefore, to understand the pathogenicity in mammals of these H5N1 viruses, we took viruses isolated from poultry (5 strains) and humans (2 strains) in Vietnam and tested their virulence in mice. The results showed that the H5N1 viruses from humans were pathogenic in mice and that one avian isolate was also pathogenic. These findings suggested that the H5N1 viruses circulating in poultry adapted during replication in humans or that strains pathogenic in mice were transmitted directly to humans.
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http://dx.doi.org/10.1292/jvms.68.735DOI Listing
July 2006

Molecular characterization of the hemagglutinin and neuraminidase genes of H5N1 influenza A viruses isolated from poultry in Vietnam from 2004 to 2005.

J Vet Med Sci 2006 May;68(5):527-31

International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Highly pathogenic H5N1 avian influenza A viruses have been spreading among domestic poultry, wild aquatic birds, and humans in many Asian countries since 2003. The largest number of patients, to date, infected with the H5N1 viruses are in Vietnam, where these viruses continue to cause outbreaks in domestic poultry. Here, we molecularly characterized the hemagglutinin and neuraminidase genes of nine H5N1 viruses isolated between January 2004 and August 2005 from domestic poultry in Vietnam. We found that several groups of highly pathogenic H5N1 avian influenza viruses are circulating among these birds, which suggests that H5N1 viruses of different lineages have been introduced into Vietnam multiple times.
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http://dx.doi.org/10.1292/jvms.68.527DOI Listing
May 2006

Avian influenza A (H5N1) in 10 patients in Vietnam.

N Engl J Med 2004 Mar 25;350(12):1179-88. Epub 2004 Feb 25.

Hospital for Tropical Diseases, Health Service of Ho Chi Minh City, Vietnam.

Background: Recent outbreaks of avian influenza A (H5N1) in poultry throughout Asia have had major economic and health repercussions. Human infections with this virus were identified in Vietnam in January 2004.

Methods: We report the clinical features and preliminary epidemiologic findings among 10 patients with confirmed cases of avian influenza A (H5N1) who presented to hospitals in Ho Chi Minh City and Hanoi, Vietnam, in December 2003 and January 2004.

Results: In all 10 cases, the diagnosis of influenza A (H5N1) was confirmed by means of viral culture or reverse transcriptase-polymerase chain reaction with primers specific for H5 and N1. None of the 10 patients (mean age, 13.7 years) had preexisting medical conditions. Nine of them had a clear history of direct contact with poultry (median time before onset of illness, three days). All patients presented with fever (temperature, 38.5 to 40.0 degrees C), respiratory symptoms, and clinically significant lymphopenia (median lymphocyte count, 700 per cubic millimeter). The median platelet count was 75,500 per cubic millimeter. Seven patients had diarrhea. In all patients, there were marked abnormalities on chest radiography. There was no definitive evidence of human-to-human transmission. Eight patients died, one patient has recovered, and one is recovering.

Conclusions: Influenza A (H5N1) infection, characterized by fever, respiratory symptoms, and lymphopenia, carries a high risk of death. Although in all 10 cases the infection appears to have been acquired directly from infected poultry, the potential exists for genetic reassortment with human influenzaviruses and the evolution of human-to-human transmission. Containment of influenza A (H5N1) in poultry throughout Asia is therefore urgently required.
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http://dx.doi.org/10.1056/NEJMoa040419DOI Listing
March 2004