Complete genome sequencing and phylogenetic analysis of dengue type 1 virus isolated from Jeddah, Saudi Arabia

Abstract

Background: Dengue viruses (DENVs) are mosquito-borne viruses which can cause disease ranging from mild fever to severe dengue infection. These viruses are endemic in several tropical and subtropical regions. Multiple outbreaks of DENV serotypes 1, 2 and 3 (DENV-1, DENV-2 and DENV-3) have been reported from the western region in Saudi Arabia since 1994. Strains from at least two genotypes of DENV-1 (Asia and America/Africa genotypes) have been circulating in western Saudi Arabia until 2006. However, all previous studies reported from Saudi Arabia were based on partial sequencing data of the envelope (E) gene without any reports of full genome sequences for any DENV serotypes circulating in Saudi Arabia.

Findings: Here, we report the isolation and the first complete genome sequence of a DENV-1 strain (DENV-1-Jeddah-1-2011) isolated from a patient from Jeddah, Saudi Arabia in 2011. Whole genome sequence alignment and phylogenetic analysis showed high similarity between DENV-1-Jeddah-1-2011 strain and D1/H/IMTSSA/98/606 isolate (Asian genotype) reported from Djibouti in 1998. Further analysis of the full envelope gene revealed a close relationship between DENV-1-Jeddah-1-2011 strain and isolates reported between 2004-2006 from Jeddah as well as recent isolates from Somalia, suggesting the widespread of the Asian genotype in this region.

Conclusions: These data suggest that strains belonging to the Asian genotype might have been introduced into Saudi Arabia long before 2004 most probably by African pilgrims and continued to circulate in western Saudi Arabia at least until 2011. Most importantly, these results indicate that pilgrims from dengue endemic regions can play an important role in the spread of new DENVs in Saudi Arabia and the rest of the world. Therefore, availability of complete genome sequences would serve as a reference for future epidemiological studies of DENV-1 viruses.

Figure 1

Dengue infected C6/36 cells. a. Uninfected C6/36 cells. b. CPE 5 days after inoculation of C6/36 cells with patient plasma.

Figure 2

Recombination events in DENV-1 strains. Schematic representation indicates the recombination events in DENV-1 strains analyzed by RDP3 package with P-value < 0.05. Continues lines indicate no recombination possibility. Analysis was performed on all sequences included in the phylogenetic tree in Figure 3. The following strains did not show any recombination events and are not shown in the figure; KJ189366-Peurto Rico-2010, KJ189304-Colombia-2005, JN054256-SriLanka-2009, KF955446-Vietnam-2008, JX669473-Brazil-2001, JQ915076-French Polynesia:Tahiti-2009, FJ850114-Nicaragua-2005, FJ810415-Venezuela-2005, JN697058-Malaysia-2005, GQ398255-Singapore-2008 and AB074761-Japan-2001.

Figure 3

Phylogenetic analysis of the full genome. The phylogenetic tree was constructed for the full genome, as indicated in the Materials and methods. Tree was generated from nucleotide alignments of sequences from the culture isolate obtained from the patient in this study and highly similar DENV-1 sequences available in the GenBank database.

Figure 4

Phylogenetic analysis of the full E gene. The phylogenetic tree was constructed for the full E gene from DENV-1-Jeddah-1-2011 isolate and E genes of other isolates from diverse regions in the world.