Comparative genome analysis between Southeast Asian and South American Zika viruses

Kochakarn, Theerarat; Kotanan, Namfon; Kümpornsin, Krittikorn; Loesbanluechai, Duangkamon; Thammasatta, Monta; Auewarakul, Prasert; Wilairat, Prapon; Chookajorn, Thanat

doi:10.1016/j.apjtm.2016.10.002

Cited by 12 publications

(9 citation statements)

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“…Although our phylogenetic analysis showed that the cases of ZIKV detected in Malaysia during 2016 originated from two different sources, it appears that all the isolates were closely related to the old ZIKV strains that have been circulating in South East Asia. On the other hand, studies have shown that the South American ZIKV isolates formed a unique clade within the Asian lineage, which was also demonstrated in our study [41, 42]. Current literature suggested that the American strain of ZIKV seemed to transmit the virus more efficiently through Aedes aegypti [43], and resulted in more serious brain damage in mice as compared to other old Asian strain of ZIKV [44].…”

Section: Discussionsupporting

confidence: 84%

Zika virus infection in Malaysia: an epidemiological, clinical and virological analysis

et al. 2019

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Background A major outbreak of the Zika virus (ZIKV) has been reported in Brazil in 2015. Since then, it spread further to other countries in the Americas and resulted in declaration of the Public Health Emergency of International Concern (PHEIC) by World Health Organization. In 2016, Singapore reported its first minor ZIKV epidemic. Malaysia shares similar ecological environment as Brazil and Singapore which may also favor ZIKV transmission. However, no ZIKV outbreak has been reported in Malaysia to date. This study aimed to discuss all confirmed ZIKV cases captured under Malaysia ZIKV surveillance system after declaration of the PHEIC; and explore why Malaysia did not suffer a similar ZIKV outbreak as the other two countries. Methods This was an observational study reviewing all confirmed ZIKV cases detected in Malaysia through the ZIKV clinical surveillance and Flavivirus laboratory surveillance between June 2015 and December 2017. All basic demographic characteristics, co-morbidities, clinical, laboratory and outcome data of the confirmed ZIKV cases were collected from the source documents. Results Only eight out of 4043 cases tested positive for ZIKV infection during that period. The median age of infected patients was 48.6 years and majority was Chinese. Two of the subjects were pregnant. The median interval between the onset of disease and the first detection of ZIKV Ribonucleic Acid (RNA) in body fluid was 3 days. Six cases had ZIKV RNA detected in both serum and urine samples. Phylogenetic analysis suggests that isolates from the 7 cases of ZIKV infection came from two clusters, both of which were local circulating strains. Conclusion Despite similar ecological background characteristics, Malaysia was not as affected by the recent ZIKV outbreak compared to Brazil and Singapore. This could be related to pre-existing immunity against ZIKV in this population, which developed after the first introduction of the ZIKV in Malaysia decades ago. A serosurvey to determine the seroprevalence of ZIKV in Malaysia was carried out in 2017. The differences in circulating ZIKV strains could be another reason as to why Malaysia seemed to be protected from an outbreak.

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Section: Discussionsupporting

confidence: 84%

Zika virus infection in Malaysia: an epidemiological, clinical and virological analysis

et al. 2019

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“…These observations were used to postulate that particular genetic variants might have been under positive selection, and thus be enriched in viral populations [ 14 , 15 , 32 ]. Based on analysis of 33 ZIKV genomes, it was questioned if the Brazilian lineage was truly derived from the Asian lineage [ 33 ]. Such conclusions must be weighed against the natural variation occurring in the viral population, and observations become more accurate with larger datasets.…”

Section: Resultsmentioning

confidence: 99%

Suggested mechanisms for Zika virus causing microcephaly: what do the genomes tell us?

et al. 2017

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BackgroundZika virus (ZIKV) is an emerging human pathogen. Since its arrival in the Western hemisphere, from Africa via Asia, it has become a serious threat to pregnant women, causing microcephaly and other neuropathies in developing fetuses. The mechanisms behind these teratogenic effects are unknown, although epidemiological evidence suggests that microcephaly is not associated with the original, African lineage of ZIKV. The sequences of 196 published ZIKV genomes were used to assess whether recently proposed mechanistic explanations for microcephaly are supported by molecular level changes that may have increased its virulence since the virus left Africa. For this we performed phylogenetic, recombination, adaptive evolution and tetramer frequency analyses, and compared protein sequences for the presence of protease cleavage sites, Pfam domains, glycosylation sites, signal peptides, trans-membrane protein domains, and phosphorylation sites.ResultsRecombination events within or between Asian and Brazilian lineages were not observed, and likewise there were no differences in protease cleavage, glycosylation sites, signal peptides or trans-membrane domains between African and Brazilian strains. The frequency of Retinoic Acid Response Element (RARE) sequences was increased in Brazilian strains. Genetic adaptation was also apparent by tetramer signatures that had undergone major changes in the past but has stabilized in the Brazilian lineage despite subsequent geographic spread, suggesting the viral population presently propagates in the same host species in various regions. Evidence for selection pressure was recognized for several amino acid sites in the Brazilian lineage compared to the African lineage, mainly in nonstructural proteins, especially protein NS4B. A number of these positively selected mutations resulted in an increased potential to be phosphorylated in the Brazilian lineage compared to the African linage, which may have increased their potential to interfere with neural fetal development.ConclusionsZIKV seems to have adapted to a limited number of hosts, including humans, during which its virulence increased. Its protein NS4B, together with NS4A, has recently been shown to inhibit Akt-mTOR signaling in human fetal neural stem cells, a key pathway for brain development. We hypothesize that positive selection of novel phosphorylation sites in the protein NS4B of the Brazilian lineage could interfere with phosphorylation of Akt and mTOR, impairing Akt-mTOR signaling and this may result in an increased risk for developmental neuropathies.Electronic supplementary materialThe online version of this article (10.1186/s12859-017-1894-3) contains supplementary material, which is available to authorized users.

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“…The first large outbreak of the Zika virus in humans was registered only in 2007 on the Pacific island of Yap, in Micronesia [ 16 ]. The same lineage, an Asian type, caused epidemics in the Pacific Islands in 2013–2014 [ 17 – 18 ]. Phylogenetic analyses revealed the Brazilian Zika virus to be closer to those circulating in French Polynesia in 2013, therefore, it might be possible that the Asian-type strains caused unreported microcephaly in the past outbreaks [ 4 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Zika might not be acting alone: Using an ecological study approach to investigate potential co-acting risk factors for an unusual pattern of microcephaly in Brazil

et al. 2018

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Zika virus infections can cause a range of neurologic disorders including congenital microcephaly. However, while Zika infections have been notified across all regions in Brazil, there has been an unusual number of congenital microcephaly case notifications concentrated in the Northeast of the country. To address this observation, we investigated epidemiological data (2014–2016) on arbovirus co-distribution, environmental and socio-economic factors for each region in Brazil. Data on arbovirus reported cases and microcephaly were collected from several Brazilian Ministry of Health databases for each Federal unit. These were complemented by environmental management, social economic and Aedes aegypti infestation index data, extracted from multiple databases. Spatial time “ecological” analysis on the number of arboviruses transmitted by Aedes mosquitoes in Brazil show that the distribution of dengue and Zika was widespread in the whole country, with higher incidence in the West-Central region. However, reported chikungunya cases were higher in the Northeast, the region also with the highest number of microcephaly cases registered. Social economic factors (human development index and poverty index) and environmental management (water supply/storage and solid waste management) pointed the Northeast as the less wealthy region. The Northeast is also the region with the highest risk of Aedes aegypti house infestation due to the man-made larval habitats. In summary, the results of our ecological analysis support the hypothesis that the unusual distribution of microcephaly might not be due to Zika infection alone and could be accentuated by poverty and previous or co-infection with other pathogens. Our study reinforces the link between poverty and the risk of disease and the need to understand the effect on pathogenesis of sequential exposure to arboviruses and co-viral infections. Comprehensive large-scale cohort studies are required to corroborate our findings. We recommend that the list of infectious diseases screened, particularly during pregnancy, be regularly updated to include and effectively differentiate all viruses from ongoing outbreaks.

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Comparative genome analysis between Southeast Asian and South American Zika viruses

Abstract: These findings may help explain the cross-reactivity of DENV antibodies to ZIKV. Thus, major caveats must be exercised in using existing diagnostic tools for ZIKV.

Cited by 12 publications

References 62 publications

Zika virus infection in Malaysia: an epidemiological, clinical and virological analysis

Zika virus infection in Malaysia: an epidemiological, clinical and virological analysis

Suggested mechanisms for Zika virus causing microcephaly: what do the genomes tell us?

Zika might not be acting alone: Using an ecological study approach to investigate potential co-acting risk factors for an unusual pattern of microcephaly in Brazil

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