Isolation of monoclonal antibodies-escape variant of dengue virus serotype 1.
BACKGROUND
During an outbreak from December 2004 to March 2005, 138 isolates of dengue virus were prospectively obtained from acute-phase serum samples of 1,067 patients with the provisional clinical diagnosis of acute dengue illness admitted to the adult wards of Hospital Tengku Ampuan Rahimah, Klang, Malaysia. Of the 138 dengue virus isolates, 87, 11, 24 and 3 were typed as dengue serotypes 1, 2, 3 and 4, respectively, by a commercial dengue virus typing kit using monoclonal antibodies (Mab). 13 dengue virus isolates could not be assigned to any specific serotype by serotyping Mab and molecular typing using dengue-type specific molecular typing primer pairs. We report the associated clinical features and limited molecular genetics of this Mab-escape dengue virus variant.


METHODS
Limited molecular characterisation of the Mab-escape dengue virus variants with respect to a few concurrently isolated dengue serotype 1 virus was performed by reverse transcriptase polymerase chain reaction (RT-PCR), followed by nucleic acid sequencing of the 500-bp dengue virus partial genomic capsid-PreM fragment.


RESULTS
The aligned nucleic acid sequence of RT-PCR products showed that these Mab-escape variants were of identical nucleic acid sequence, and shared the highest sequence homology (99 percent) with dengue virus serotype 1 (GeneBank accession No. AB178040) isolated from a Japanese patient in 2004. Though these Mab-escape dengue virus variants were noted to replicate to a 2-log higher titre than the current circulating dengue virus serotype 1, there was no significant difference between these variants and the currently circulating dengue virus serotype 1 with respect to disease severity (dengue fever versus dengue haemorrhagic fever) and clinical features.


CONCLUSIONS
There was no significant difference in the proportion of patients developing dengue haemorrhagic fever following acute infection by Mab-escape dengue virus 1 variant in comparison with infection by the conventional dengue virus 1. Similarly, there was no significant difference in the pattern of clinical presentations following acute infection by the two different strains of virus.
Chua
S K
SK
Hospital Tengku Ampuan Rahimah, Jalan Banting, Klang 41200, Malaysia. chuakawbing@yahoo.com.sg
Selvanesan
S
S
Sivalingam
B
B
Chem
Y K
YK
Norizah
I
I
Zuridah
H
H
Kumarasamy
V
V
Chua
K B
KB
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D003716:Dengue Virus / Q000145:classification* / Q000302:isolation & purification*; D004196:Disease Outbreaks; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008969:Molecular Sequence Data; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*; D012703:Serotyping; D019595:Severe Dengue / Q000453:epidemiology / Q000821:virology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D012367:RNA, Viral