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Authors = Sujan Shresta

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15 pages, 2545 KB  
Article
Acute-phase Serum Cytokine Levels and Correlation with Clinical Outcomes in Children and Adults with Primary and Secondary Dengue Virus Infection in Myanmar between 2017 and 2019
by Khine Mya Nwe, Mya Myat Ngwe Tun, Theingi Win Myat, Chris Fook Sheng Ng, Moh Moh Htun, Htin Lin, Nang Sarm Hom, Aung Min Soe, Annie Elong Ngono, Shinjiro Hamano, Kouichi Morita, Kyaw Zin Thant, Sujan Shresta, Hlaing Myat Thu and Meng Ling Moi
Pathogens 2022, 11(5), 558; https://doi.org/10.3390/pathogens11050558 - 9 May 2022
Cited by 5 | Viewed by 4101
Abstract
The dengue virus (DENV) has been endemic in Myanmar since 1970, causing outbreaks every 2–3 years. DENV infection symptoms range from mild fever to lethal hemorrhage. Clinical biomarkers must be identified to facilitate patient risk stratification in the early stages of infection. We [...] Read more.
The dengue virus (DENV) has been endemic in Myanmar since 1970, causing outbreaks every 2–3 years. DENV infection symptoms range from mild fever to lethal hemorrhage. Clinical biomarkers must be identified to facilitate patient risk stratification in the early stages of infection. We analyzed 45 cytokines and other factors in serum samples from the acute phase of DENV infection (within 3–5 days of symptom onset) from 167 patients in Yangon, Myanmar, between 2017 and 2019. All of the patients tested positive for serum DENV nonstructural protein 1 antigen (NS1 Ag); 78.4% and 62.9% were positive for immunoglobulin M (IgM) and G (IgG), respectively; and 18.0%, 19.8%, and 11.9% tested positive for serotypes 1, 3, and 4, respectively. Although the DENV-4 viral load was significantly higher than those of DENV-1 or DENV-3, disease severity was not associated with viral load or serotype. Significant correlations were identified between disease severity and CCL5, SCF, PDGF-BB, IL-10, and TNF-α levels; between NS1 Ag and SCF, CCL5, IFN-α, IL-1α, and IL-22 levels; between thrombocytopenia and IL-2, TNF-α, VEGF-D, and IL-6 levels; and between primary or secondary infection and IL-2, IL-6, IL-31, IL-12p70, and MIP-1β levels. These circulating factors may represent leading signatures in acute DENV infections, reflecting the clinical outcomes in the dengue endemic region, Myanmar. Full article
(This article belongs to the Special Issue Virus-Host Interactions and Pathogenesis of Arbovirus)
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16 pages, 2974 KB  
Article
Emergence of a Novel Dengue Virus 3 (DENV-3) Genotype-I Coincident with Increased DENV-3 Cases in Yangon, Myanmar between 2017 and 2019
by Aung Min Soe, Mya Myat Ngwe Tun, Takeshi Nabeshima, Theingi Win Myat, Moh Moh Htun, Htin Lin, Nang Sarm Hom, Shingo Inoue, Khine Mya Nwe, Lynn Pa Pa Aye, Mizuki Fukuta, Kyaw Zin Thant, Futoshi Hasebe, Kouichi Morita, Sujan Shresta, Hlaing Myat Thu and Meng Ling Moi
Viruses 2021, 13(6), 1152; https://doi.org/10.3390/v13061152 - 16 Jun 2021
Cited by 23 | Viewed by 4662
Abstract
Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV strains are identified and monitored, and that their transmission efficiency and association [...] Read more.
Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV strains are identified and monitored, and that their transmission efficiency and association with disease severity is understood. In this study, we analyzed DENV-1, DENV-2, DENV-3, and DENV-4 serotypes in 1235 serum samples collected in Myanmar between 2017 and 2019. Whole-genome sequencing of DENV-1–4 demonstrated that most DENV-1–4 strains had been circulating in Myanmar for several years. We also identified the emergence of DENV-3 genotype-I in 2017 samples, which persisted through 2018 and 2019. The emergence of the strain coincided with a period of increased DENV-3 cases and marked changes in the serotype dynamics. Nevertheless, we detected no significant differences between serum viral loads, disease severity, and infection status of individuals infected with different DENV serotypes during the 3-year study. Our results not only identify the spread of a new DENV-3 genotype into Yangon, Myanmar, but also support the importance of DENV evolution in changing the epidemic dynamics in endemic regions. Full article
(This article belongs to the Special Issue Viral Infections in Developing Countries)
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9 pages, 209 KB  
Review
Development of Zika Virus Vaccines
by Huda Makhluf and Sujan Shresta
Vaccines 2018, 6(1), 7; https://doi.org/10.3390/vaccines6010007 - 18 Jan 2018
Cited by 28 | Viewed by 10286
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré [...] Read more.
Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant women is associated with fetal abnormalities such as microcephaly, and infection of adults can lead to Guillain–Barré syndrome, an autoimmune disease characterized by neurological deficits. Although there are currently licensed vaccines for other flaviviruses, there remains an urgent need for preventative vaccines against ZIKV infection. Herein we describe the current efforts to accelerate the development of ZIKV vaccines using various platforms, including live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in silico-predicted immunogenic viral epitopes. Many of these approaches have leveraged lessons learned from past experience with Dengue and other flavivirus vaccines. Full article
(This article belongs to the Special Issue Vaccines against Emerging and Reemerging Viral Diseases of Humans and Animals)
24 pages, 984 KB  
Article
A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
by Kelly L. Warfield, Emily Plummer, Dominic S. Alonzi, Gary W. Wolfe, Aruna Sampath, Tam Nguyen, Terry D. Butters, Sven G. Enterlein, Eric J. Stavale, Sujan Shresta and Urban Ramstedt
Viruses 2015, 7(5), 2404-2427; https://doi.org/10.3390/v7052404 - 13 May 2015
Cited by 27 | Viewed by 7762
Abstract
Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases [...] Read more.
Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher’s disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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