Lee Tze Chuan Raphael

Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals

Published date : 03 Jul 2018

A total of 13672 viruses, collected by World Health Organization recognised National Influenza Centres between May 2016 and May 2017, were assessed for neuraminidase inhibitor susceptibility by four WHO Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance Epidemiology and Control of Influenza. The 50% inhibitory concentration (IC50) was determined for oseltamivir and zanamivir for all viruses, and for peramivir and laninamivir in a subset (n = 8457).

type
Journal Paper
journal
Antiviral Research 2018 Jul 3;157:38-46. doi: 10.1016/j.antiviral.2018.07.001
Impact Factor
4.307

Inter-Species Host Gene Expression Differences in Response to Human and Avian Influenza A Virus Strains

Published date : 01 Nov 2017

Low pathogenic avian influenza (LPAI) viruses are a source of sporadic human infections and could also contribute to future pandemic outbreaks but little is known about inter-species differences in the host responses to these viruses. Here, we studied host gene expression signatures of cell lines from three species (human, chicken, and canine) in response to six different viruses (H1N1/WSN, H5N2/F59, H5N2/F118, H5N2/F189, H5N3 and H9N2).

type
Journal Paper
journal
International Journal of Molecular Sciences, Vol. 18, Issue 11, doi: 10.3390/ijms18112295
Impact Factor
3.226

HIV-1 subtype CRF01_AE and B differ in utilization of low levels of CCR5, Maraviroc susceptibility and potential N-glycosylation sites

Published date : 09 Oct 2017

HIV subtypes not only predominate in different geographical regions but also differ in key phenotypic characteristics. To determine if genotypic and/or phenotypic differences in the Envelope (Env) glycoprotein can explain subtype related differences, we cloned 37 full length Envs from Subtype B and AE HIV infected individuals from Singapore. Our data demonstrates that CRF01_AE Envs have lower Potential N Glycosylation Sites and higher risk of ×4 development. Phenotypically, CRF01_AE were less infectious than subtype B Envs in cells expressing low levels of CCR5.

type
Journal Paper
journal
Virology, 512, 2017 December, Pg 222-233, doi: 10.1016/j.virol.2017.09.02
Impact Factor
3.353

South-east Asian Zika virus strain linked to cluster of cases in Singapore, August 2016

Published date : 22 Sep 2016

Zika virus (ZIKV) is an ongoing global public health emergency with 70 countries and territories reporting evidence of ZIKV transmission since 2015. On 27 August 2016, Singapore reported its first case of local ZIKV transmission and identified an ongoing cluster. Here, we report the genome sequences of ZIKV strains from two cases and find through phylogenetic analysis that these strains form an earlier branch distinct from the recent large outbreak in the Americas.

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Journal Paper
journal
Eurosurveillance, Volume 21, Issue 38, 22 September 2016, DOI: http://dx.doi.org/10.2807/1560-7917.ES.2016.21.38.30347
Impact Factor
5.8

Dynamic convergent evolution drives the passage adaptation across 48 years’ history of H3N2 influenza evolution

Published date : 07 Sep 2016

Influenza viruses are often propagated in a diverse set of culturing media and additional substitutions known as passage adaptation can cause extra evolution in the target strain, leading to ineffective vaccines. Using 25,482 H3N2 HA1 sequences curated from Global Initiative on Sharing All Influenza Data and National Center for Biotechnology Information databases, we found that passage adaptation is a very dynamic process that changes over time and evolves in a seesaw like pattern.

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Journal Paper
journal
Molecular Biology and Evolution, 2016 Sep 7, doi: 10.1093/molbev/msw190
Impact Factor
13.6

Molecular and biochemical characterization of the NS1 protein of non-cultured influenza B virus strains circulating in Singapore

Published date : 25 Aug 2016

In this study we compared the NS1 protein of Influenza B/Lee/40 and several non-cultured Influenza B virus clinical strains detected in Singapore. In B/Lee/40 virus-infected cells and in cells expressing the recombinant B/Lee/40 NS1 protein a full-length 35 kDa NS1 protein and a 23 kDa NS1 protein species (p23) were detected.

type
Journal Paper
journal
Microbial Genomics 2016 Aug; 2(8): e000082, doi: 10.1099/mgen.0.000082

Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014–2015

Published date : 03 Jun 2016

The World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza (WHO CCs) tested 13,312 viruses collected by WHO recognized National Influenza Centres between May 2014 and May 2015 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Ninety-four per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe.

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Journal Paper
journal
Antiviral Research, 2016, http://dx.doi.org/10.1016/j.antiviral.2016.06.001
Impact Factor
4.909

HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc

Published date : 24 Mar 2016

Variability in CCR5 levels in the human population is suggested to affect virus evolution, fitness and the course of HIV disease. We previously demonstrated that cell surface CCR5 levels directly affect HIV Envelope mediated bystander apoptosis. In this study, we attempted to understand HIV evolution in the presence of low levels of CCR5, mimicking the limiting CCR5 levels inherent to the host. HIV-1 adaptation in a T cell line expressing low levels of CCR5 resulted in two specific mutations; N302Y and E172K.

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Journal Paper
journal
Virology. 2016 Mar 24; 493:86-99. doi: 10.1016/j.virol.2016.03.010
Impact Factor
3.2

Discovery of Influenza A Virus Sequence Pairs and Their Combinations for Simultaneous Heterosubtypic Targeting that Hedge against Antiviral Resistance

Published date : 15 Jan 2016

The multiple circulating human influenza A virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. The capacity to drug most RNAs motivates the investigation on viral RNA targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans–H1N1, 2009 pandemic H1N1, H3N2, H5N1 and H7N9, were used to identify 1,183 conserved RNA target sequences (≥15-mer) in the internal segments.

type
Journal Paper
journal
PLOS Computational Biology, 15 Jan 2016, doi: 10.1371/journal.pcbi.1004663
Impact Factor
4.829

Influenza A(H5N8) Virus Similar to Strain in Korea Causing Highly Pathogenic Avian Influenza in Germany

Published date : 01 May 2015

Highly pathogenic avian influenza (H5N8) virus, like the recently described H5N8 strain from Korea, was detected in November 2014 in farmed turkeys and in a healthy common teal (Anas crecca) in northeastern Germany. Infected wild birds possibly introduced this virus.

type
Journal Paper
journal
Emerging Infectious Diseases, Vol. 21, No. 5, May 2015, Pg 860-863, doi: 10.3201/eid2105.141897, PMID: 25897703
Impact Factor
7.327