An Epidemic of Dengue Virus Serotype-4 during the 2015 - 2017: the Emergence of a Novel Genotype IIa of DENV-4 in the Philippines.

Volume 72 no 6, p.413-419, 2019. Page 418, Acknowledgments "We would like to thank all staff and members of the Department of Virology, NEKKEN, Nagasaki University, Japan for providing technical support and advice. Our special thanks to the staff of the Pavilion II and the Central Laboratory of San Lazaro Hospital for their kind assistance during patient recruitment and data collection. We are also very grateful for the support of the Senior Vice President and Head of Research and Biotechnology (R&B) Group of St. Luke's Medical Center, Dr. Isaac David E. Ampil II. Finally, our sincere thanks to the members of R&B's dengue research group for kindly preparing the samples to be transported to NEKKEN." should read "This research was supported by grants from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP18fm0108001, JP19fm0108001 (Japan Initiative for Global Research Network on Infectious Diseases (J-GRID)), AMED Research on Emerging and Re-emerging Infectious Diseases (19fk0108035j0003) and e-ASIA Joint Research Program and; Philippine Council for Health Research and Development (PCHRD) of the Department of Science and Technology (DOST), Philippines, with partial support from the Research and Biotechnology of St. Luke's Medical Center (R&B-SLMC), Philippines (Project No. 07-024). Funders have no role in the study design, data collection, and interpretation, or the decision to submit this work for publication. We would like to thank all staff and members of the Department of Virology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Japan, for providing technical support and advice. Our special thanks to the staff of the Pavilion II and the Central Laboratory of San Lazaro Hospital for their kind assistance during patient recruitment and data collection. We are also very grateful for the support of the Senior Vice President and Head of Research and Biotechnology (R&B) Group of St. Luke's Medical Center, Dr. Isaac David E. Ampil II. Finally, our sincere thanks to the members of R&B's Dengue Research Group for kindly preparing the samples to be transported to NEKKEN."

An Epidemic of Dengue Virus Serotype-4 during the 2015 - 2017: the Emergence of a Novel Genotype IIa of DENV-4 in the Philippines.

Dengue remains a major public health problem in the Philippines. In this study, we determined the circulating dengue serotypes in the Philippines during the 2015-2017 outbreaks using a total of 678 serum samples from 537 individual dengue patients. Following an increase in the number of DENV-4 patients in recent years, we conducted a comprehensive molecular and epidemiology analysis on the DENV-4 strains isolated recently in the Philippines. Two genotypes of DENV-4 have been isolated in the Philippines since 1956: GI and GIIa. The GIIa DENV strains that were isolated in the present study were closely related to a distinct group of GIIa strains that were isolated from the Philippines in 2004. A majority of the isolates of this sub-group have been identified in the Philippines, suggesting that this lineage may have been introduced in the Philippines, and evolved to form the distinct sub-group within GIIa strains. The increase in DENV-4 activity also coincided with the appearance of the GIIa subgroup and the phasing-out of the GI lineage in the Philippines. Overall, our study demonstrates a shift in DENV-4 genotype and epidemic dynamics in a hyperendemic region, suggesting the importance of DENV genetic evolution in establishing and sustaining transmission.

A Simple Mechanism Based on Amino Acid Substitutions is not a Critical Determinant of High Mortality of Japanese Encephalitis Virus Infection in Mice.

For the development of effective treatment strategies for Japanese encephalitis (JE), it is important to identify the viral factors causing severe disease during JE virus (JEV) infection. In this study, we assessed whether amino acid substitutions are critical factors for higher mortality of JaTH160 compared with JaOArS982 in mice using the technique of infectious cDNA clones. We raised the possibility that two amino acids of C124 and NS3482 of JaTH160 may contribute to increased mortality in mice. However, simultaneous substitutions of these amino acids did not significantly increase the virulence of JaOArS982, suggesting that high mortality due to JaTH160 viral infection cannot be simply attributed to the specific amino acids. Multiple and complex, but not simple, mechanisms may induce the high mortality of JaTH160 infection in mice.

Inhibitory effect of the green tea molecule EGCG against dengue virus infection.

Dengue virus (DENV) infection is a major public health problem worldwide; however, specific antiviral drugs against it are not available. Hence, identifying effective antiviral agents for the prevention of DENV infection is important. In this study, we showed that the reportedly highly biologically active green-tea component epigallocatechin gallate (EGCG) inhibited dengue virus infection regardless of infecting serotype, but no or minimal inhibition was observed with other flaviviruses, including Japanese encephalitis virus, yellow fever virus, and Zika virus. EGCG exerted its antiviral effect mainly at the early stage of infection, probably by interacting directly with virions to prevent virus infection. Our results suggest that EGCG specifically targets DENV and might be used as a lead structure to develop an antiviral drug for use against the virus.