Multiple recombinants in two dengue virus, serotype-2 isolates from patients from Oaxaca, Mexico

Abstract

BackgroundDengue (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.ResultsTo 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.ConclusionsThis 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.

Population dynamics of DENV-1 genotype V in Brazil is characterized by co-circulation and strain/lineage replacement

“…However, the co-circulation of different DENV populations, including different genotypes, is a factor that increases the chances of the occurrence of mixed infections both in the mosquito vector and in the human host [45,46], which in turn could favor the occurrence of recombination, as observed in Brazil, where different DENV-1 lineages from genotype V have been co-circulating. Although it is not possible to determine whether recombination has occurred in the mosquito vector, the human host or in vitro (during virus replication in C6/36 cells), or when these events might have occurred among the Brazilian DENV-1 isolates, recombination events have already been described in natural populations, including intra and inter-genotypic recombinants, as described for DENV-1 and DENV-2 [19,45,[47][48][49]. Although it is likely that most recombinant events are deleterious and thus eliminated by purifying selection, some of them could result in an increase in the fitness of the virus.…”

“…Although it is likely that most recombinant events are deleterious and thus eliminated by purifying selection, some of them could result in an increase in the fitness of the virus. These events could have important implications for virus evolution, virulence, and diagnosis and for the development of vaccines and therapeutic drugs [45,47,49].…”

Arboviruses: Variations on an Ancient Theme

“…These strains displayed recombination in the prM-E and E-NS1 regions, incorporating genome sequence from parental strains belonging to the Asian/American and cosmopolitan genotypes. Moreover, recombination of the E gene (region between 906 and 1047 nucleotides) was also found for the infectious clone MEX_OAX_165607_05 (isolated from the MEX_OAX_1656_05 strain) incorporating genome sequences from the American genotype [143]. Finally, a recent study identified a recombinant DENV-1 strain isolated in Guandong, China, with three regions of recombination in the prM-E junction, NS1 and NS3 regions [144].…”

“…Another study performed in 2007 showed that regions of the E gene underwent recombination in a patient harboring a mixed infection of DENV-1 [139]. Recombination was also reported in the Americas between two DENV-2 strains that circulated in Oaxaca, Mexico, in 2005-2006 [143]. These strains displayed recombination in the prM-E and E-NS1 regions, incorporating genome sequence from parental strains belonging to the Asian/American and cosmopolitan genotypes.…”

Unique safety issues associated with virus-vectored vaccines: Potential for and theoretical consequences of recombination with wild type virus strains

“…For RNA viruses containing segmented genomes, gene exchange occurs primarily through reassortment of individual parental genome segments into progeny viruses, however intragenic recombination has also been reported for the segmented orthomyxoviruses, reoviruses and bunyaviruses [12][13][14][15][16]. Recombination has been observed in several singlestranded RNA (ssRNA) virus families representing both positive and negative sense genomes both in the laboratory and in the wild; picornaviruses, coronaviruses, togaviruses and retroviruses, all with positive sense ssRNA genomes, display relatively efficient recombination [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The frequency of recombination among negative sense RNA viruses (excluding reassortment of segmented genomes) seems to be relatively low [31].…”