Evolution and heterogeneity of multiple serotypes of Dengue virus in Pakistan, 2006–2011

Virology Journal

Erum Khan²  Lee-Ching Ng¹  Zahra Hasan²  Kim-Sung Lee¹  Hapuarachchige Chanditha Hapuarachchi¹  Amna Nasir²  Carmen Koo¹ 

[1] Environmental Health Institute, National Environment Agency, [as part of its work as a] WHO Collaborating Centre for Reference and Research of Arbovirus and their Associated Vectors, 11, Biopolis Way, #06-05-08, 138667 Singapore, Singapore;Department of Pathology Microbiology, Aga Khan University, Stadium Road, P. O. Box 3500, Karachi 74800, Pakistan

关键词: Pakistan;    Genome;    Phylogenetics;    Molecular epidemiology;    Diversity;    Evolution;    Dengue;   

Others  :  821730
DOI  :  10.1186/1743-422X-10-275

 received in 2013-05-16, accepted in 2013-08-30,  发布年份 2013

【 摘 要 】

Background

Even though dengue has been recognized as one of the major public health threats in Pakistan, the understanding of its molecular epidemiology is still limited. The genotypic diversity of Dengue virus (DENV) serotypes involved in dengue outbreaks since 2005 in Pakistan is not well studied. Here, we investigated the origin, diversity, genetic relationships and geographic distribution of DENV to understand virus evolution during the recent expansion of dengue in Pakistan.

Methods

The study included 200 sera obtained from dengue-suspected patients from 2006 to 2011. DENV infection was confirmed in 94 (47%) sera by a polymerase chain reaction assay. These included 36 (38.3%) DENV-2, 57 DENV-3 (60.6%) and 1 DENV-4 (1.1%) cases. Sequences of 13 whole genomes (6 DENV-2, 6 DENV-3 and 1 DENV-4) and 49 envelope genes (26 DENV-2, 22 DENV-3 and 1 DENV-4) were analysed to determine the origin, phylogeny, diversity and selection pressure during virus evolution.

Results

DENV-2, DENV-3 and DENV-4 in Pakistan from 2006 to 2011 shared 98.5-99.6% nucleotide and 99.3-99.9% amino acid similarity with those circulated in the Indian subcontinent during the last decade. Nevertheless, Pakistan DENV-2 and DENV-3 strains formed distinct clades characterized by amino acid signatures of NS2A-I116T + NS5-K861R and NS3-K590R + NS5-S895L respectively. Each clade consisted of a heterogenous virus population that circulated in Southern (2006–2009) and Northern Pakistan (2011).

Conclusions

DENV-2, DENV-3 and DENV-4 that circulated during 2006–2011 are likely to have first introduced via the southern route of Pakistan. Both DENV-2 and DENV-3 have undergone in-situ evolution to generate heterogenous populations, possibly driven by sustained local DENV transmission during 2006–2011 periods. While both DENV-2 and DENV-3 continued to circulate in Southern Pakistan until 2009, DENV-2 has spread in a Northern direction to establish in Punjab Province, which experienced a massive dengue outbreak in 2011.

【 授权许可】

   
2013 Koo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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