Department of Genetics and Molecular Biology, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Av, Instituto Politecnico Nacional 2508, San Pedro Zacatenco, Mexico.
BMC Microbiol. 2009 Dec 15;9:260. doi: 10.1186/1471-2180-9-260.
Dengue (DEN) is a serious cause of mortality and morbidity in the world including Mexico, where the infection is endemic. One of the states with the highest rate of dengue cases is Oaxaca. The cause of DEN is a positive-sense RNA virus, the dengue virus (DENV) that evolves rapidly increasing its variability due to the absence of a repair mechanism that leads to approximately one mutational event per genome replication; which results in enhancement of viral adaptation, including the escape from host immune responses. Additionally, recombination may play a role in driving the evolution of DENV, which may potentially affect virulence and cause host tropism changes. Recombination in DENV has not been described in Mexican strains, neither has been described the relevance in virus evolution in an endemic state such as Oaxaca where the four serotypes of DENV are circulating.
To study whether there are isolates from Oaxaca having recombination, we obtained the sequence of 6 different isolates of DENV-2 Asian/American genotype from the outbreak 2005-6, one clone of the C(91)-prM-E-NS1(2400) structural genes, and 10 clones of the E gene from the isolate MEX_OAX_1656_05. Evidence of recombination was found by using different methods along with two softwares: RDP3 and GARD. The Oaxaca MEX_OAX_1656_05 and MEX_OAX_1038_05 isolates sequenced in this study were recombinant viruses that incorporate the genome sequence from the Cosmopolitan genotype. Furthermore, the clone of the E gene namely MEX_OAX_165607_05 from this study was also recombinant, incorporating genome sequence from the American genotype.
This is the first report of recombination in DENV-2 in Mexico. Given such a recombinant activity new genomic combinations were produced, this could play a significant role in the DENV evolution and must be considered as a potentially important mechanism generating genetic variation in this virus with serious implications for the vaccines and drugs formulation as occurs for other viruses like poliovirus, influenza and HIV.
登革热（DEN）是全球范围内导致死亡率和发病率的一个严重原因，包括流行登革热的墨西哥。登革热病例发生率最高的州之一是瓦哈卡州。登革热的病原体是一种正链 RNA 病毒，即登革病毒（DENV），由于缺乏修复机制，该病毒进化迅速，导致每个基因组复制就会发生大约一次突变事件；这导致病毒适应性增强，包括逃避宿主免疫反应。此外，重组可能在驱动 DENV 的进化中发挥作用，这可能会潜在影响病毒的毒力并导致宿主嗜性改变。在墨西哥株中尚未描述 DENV 的重组，也未描述在像瓦哈卡这样流行的州中病毒进化的相关性，在那里，四种血清型的 DENV 正在传播。
为了研究瓦哈卡是否有重组的分离株，我们从 2005-6 年的疫情中获得了 6 种不同的 DENV-2 亚洲/美洲基因型的分离株序列，一个 C(91)-prM-E-NS1(2400) 结构基因的克隆，以及从分离株 MEX_OAX_1656_05 获得的 10 个 E 基因克隆。使用不同的方法以及两种软件：RDP3 和 GARD，发现了重组的证据。在本研究中测序的瓦哈卡 MEX_OAX_1656_05 和 MEX_OAX_1038_05 分离株是重组病毒，它们包含来自世界性基因型的基因组序列。此外，本研究中的 E 基因克隆 MEX_OAX_165607_05 也是重组病毒，包含来自美洲基因型的基因组序列。
这是墨西哥首次报道 DENV-2 中的重组。鉴于这种重组活动产生了新的基因组组合，这可能在 DENV 的进化中发挥重要作用，并且必须被视为一种潜在的重要机制，在这种病毒中产生遗传变异，这对疫苗和药物的配方有严重影响，就像对其他病毒如脊髓灰质炎病毒、流感病毒和 HIV 一样。
