Tuesday, 22 October 2013

DENV-5: virus from the jungle comes to humans?

Earlier today I posted on a conference announcement by Dr Nikos Vasilakis of a 5th human dengue virus (DENV) discovery, "the first new dengue virus type in 50 years"

Click to enlarge. An alignment of the prototypical known 4 dengue virus 
complete genome sequences. The GenBank accession number is shown next 
to the serotype's name. They share 68.9% oligonucleotide identity. 
Aligned using Geneious 6.1.6. Thanks to Prof Paul Young for identifying prototypes. 
Feel free to use the graphic with acknowledgement to VDU.
Weeeell. There is more to understanding that headline than I initially thought. 

Turns out, and please excuse the complete ignorance of dengue literature in my earlier post, dengue coming to humans from the jungle (mosquito to non-human primate, occasionally spilling over to humans; the so-called sylvatic cycle) is not an entirely new thing. Jungle? What am I on about? DENV-5 is a new sylvatic serotype, and it must be a pretty genetically and antigenically distinct one at that, in order to get a new number. 


Dr Vasilakis has written about sylvatic spillovers previously and in great detail - see this article in Nature Reviews|Microbiology from 2011. One comment was particularity interesting...



...recent experimental evidence indicates that little or no adaptive barrier exists to the emergence of sylvatic DENV in the human population

Whether this holds true for DENV-5 remains to be defined but we know this new serotype (it elicted a very distinct antibody response in infected monkeys from that due to DENV1-4) was isolated from a human in Malaysia during 2007.

Sylvatic dengue viruses have infected humans before but there have been no sustained epidemics and they seem to have been related to 1 of the 4 serotypes currently endemic in humans. 


One example, published in PLoS Neglected Tropical Diseases, sequenced the complete genome of a distinct sylvatic DENV-2 serotype isolate that caused dengue haemorrhagic fever (DHF) in a male in Malaysia in 2008. This was the first report of a sylvatic DENV causing DHF in a human. This ancestor of the human lineage DENV-2 was genetically related to a 1970 isolate (P8-1407) also obtained from Malaysia (where Gulden is endemic), after it infected a "sentinel" monkey. Such animals are kept in an area and sampled to see if they have become infected - a way of measuring mosquito and haemorrhagic virus activity in this case.


Another example includes a sylvatic DENV-1 from 2005 isolated in Malaysia and similar to a 1972 sylvatic DENV-1 isolate (P72_1244). 


I hope that adds some value to my earlier post.


Also see Crawford Killian's post on this topic from 2011.