Phylogenetic analysis of partial pre-membrane and envelope sequences of dengue viruses circulating in India

Abstract

A B S T R A C TObjective: Phylogenetic characteristics of circulating Indian dengue viruses (DENV) were analysed using partial pre-membrane (PrM) and envelope (E) sequences. An immunodominant region was analysed for mutations, and alignment with common DENV PCR primers and probes was determined. Methods: Published Indian PrM and E DENV sequences were analysed with hitherto unpublished PrM sequences from this study site. Alignments of DENV were checked for mutations in an immunodominant region and against the commonly used PCR primers and probes. Results: All four serotypes of DENV circulate in India. Genotype (G) GIII and GI of DENV-1 co-circulated in the south with significant PrM mutations before and after 2012. DENV-2 American genotype was first reported after which the Cosmopolitan genotype co-circulated with it in the southwest. The Cosmopolitan strain has been the only DENV-2 genotype circulating, although an Asian American genotype was recently reported. Significant mutations were found in the E region of DENV-2 strains. DENV-3 strains were GIII across the country. DENV-4 GI from the south and west has now spread across India. No significant mutations were found for DENV-3 or DENV-4. Indian strains showed mutations in an immunodominant region of the E gene and in the regions targeted by commonly used PCR primers and probes. Conclusions: The genetic variability of Indian DENV with co-circulation of multiple genotypes suggests that genotype surveillance is crucial to determining the composition of dengue vaccines and understanding their contribution to epidemiology, virus fitness and pathogenesis. Some mutations seen in an immunodominant region of the E gene may allow these viruses to evade host immune cells. The mutations in the regions targeted by commonly used primers and probes necessitate higher degeneracy.

Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile

“…This indicates the parental strains are in existence without any prominent outbreaks. In Tamil Nadu till 2015, strains of DENV-4 fall under Clade C of GI ( Kasirajan et al., 2019 ), and in this study, the strains isolated in 2017 and after fall into Clade D of GI. Taken together, there is a shift in Clade C to D of DENV-4 that might be due to selection pressure.…”

“…The Clade D strains diverge from other genotype GI-GVI (including sylvatic) with a range of 0.013±0.005 to 0.158±0.029, and within group of about 0.004 ± 0.001 ( Tables 2 , 3 ). Majority of the strains isolated from various parts of India from 2007 to 2016 fall into Clade C ( Cecilia et al., 2011 ; Kumar et al., 2013 ; Ahamed et al., 2019 ; Kasirajan et al., 2019 ); and the strains isolated in 2017 and after (this study) in India seem to fall under the Clade D, which is an evidence for viral fitness of these strains; however, the diversity of selection should be studied in context to it.…”

“… Sierra and colleagues (2012) reported homotypic dengue (DENV-1/2/3) infection increases IL-10 than heterotypic infection. In Tamil Nadu, circulation of DENV-2 was reported till 2017 ( Kasirajan et al., 2019 ), and it is possible that the homotypic DENV-2-infected patient may contribute to the increased IL-10 in DENV-2 DF, while the heterotypic DENV-4 (a naïve population) infection has reduced IL-10.…”

“…Global evolutionary history shows the DENV-2 transmission routes are from South America to the Caribbean and East and South Asia to Puerto Rico (Wei and Li, 2017). In India, several studies (Kumar et al, 2010;Dash et al, 2013;Kasirajan et al, 2019) show that strains before 1971 (1956)(1957)(1958)(1959)(1960)(1961)(1962)(1963)(1964)(1965)(1966)(1967)(1968)(1969)(1970)(1971) belong to the American genotype, which has been replaced by Cosmopolitan genotype (i.e., 1971-till date). Taken together, our isolates show the establishment of Cosmopolitan genotype, and further, the DENV-2 isolates were introduced from North India to Tamil Nadu via Andhra Pradesh and Kerala.…”

Evolution, heterogeneity and global dispersal of cosmopolitan genotype of Dengue virus type 2

“…The earliest DENV-2 sequences from India belong to the American genotype, which was subsequently replaced by the cosmopolitan genotype in early 1970s 89 . Even the earliest cosmopolitan genotype sequences from India belong to the Indian sub-continent lineage 89 , and the same lineage dominated during subsequent outbreaks in different regions 66 , 90 – 94 , suggesting the important epidemiological role played by this lineage in India. Indian sub-continent lineage subsequently spread to other countries in Indian sub-continent, Southeast Asia, Middle East and Africa.…”