Koo Carmen, Nasir Amna, Hapuarachchi Hapuarachchige Chanditha, Lee Kim-Sung, Hasan Zahra, Ng Lee-Ching, Khan Erum
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.
Virol J. 2013 Sep 4;10:275. doi: 10.1186/1743-422X-10-275.
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.
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.
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).
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.
尽管登革热已被公认为巴基斯坦主要的公共卫生威胁之一，但对其分子流行病学的了解仍然有限。2005年以来巴基斯坦登革热疫情中涉及的登革病毒（DENV）血清型的基因型多样性尚未得到充分研究。在此，我们调查了DENV的起源、多样性、遗传关系和地理分布，以了解巴基斯坦近期登革热疫情扩散期间病毒的进化情况。
该研究纳入了2006年至2011年期间从疑似登革热患者中采集的200份血清。通过聚合酶链反应检测在94份（47%）血清中确认了DENV感染。其中包括36例（38.3%）DENV - 2、57例（60.6%）DENV - 3和1例（1.1%）DENV - 4。分析了13个全基因组序列（6个DENV - 2、6个DENV - 3和1个DENV - 4）和49个包膜基因序列（26个DENV - 并确定病毒进化过程中的起源、系统发育、多样性和选择压力。
2006年至2011年期间巴基斯坦的DENV - 2、DENV - 3和DENV - 4与过去十年在印度次大陆传播的病毒株核苷酸相似性为98.5 - 99.6%，氨基酸相似性为99.3 - 99.9%。然而，巴基斯坦的DENV - 2和DENV - 3毒株形成了不同的分支，分别以NS2A - I116T + NS5 - K861R和NS3 - K590R + NS5 - S895L的氨基酸特征为特征。每个分支都由在巴基斯坦南部（2006 - 2009年）和北部（2011年）传播的异质病毒群体组成。
2006 - 2011年期间传播的DENV - 2、DENV - 3和DENV - 4可能首先通过巴基斯坦的南部路线传入。DENV - 2和DENV - 3都经历了原地进化，产生了异质群体，这可能是由2006 - 2011年期间当地持续的DENV传播驱动的。虽然DENV - 2和DENV - 3在2009年之前一直在巴基斯坦南部传播，但DENV - 2已向北传播并在旁遮普省定殖，该省在2011年经历了大规模的登革热疫情。
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