What do influenza, measles, rabies, encephalitis, Lassa fever, Ebola, and Hantaan have in common?
All of these diverse infectious diseases, and many others, owe their existence to negative, single-strand RNA viruses. Some of them are members of a predaceous viral family — the Bunyaviruses.
Negative-strand RNA viruses have single-stranded genomic RNAs that are complementary to viral messenger RNAs. Molecular virologists have been hot on the genomic trail of these treacherous pathogens for years.
Until now, one group in particular of these Bunyaviruses has frustrated efforts to obtain their DNA infectious clones. These recalcitrant viruses have their outsize genomes divided into three segments — L (large), M (medium) and S (small). Each encodes a different viral protein:
The L RNA segment, (6,875 nucleotides long), encodes viral RNA polymerase; M, (4,458 nucleotides), two virion glycoproteins; S, (961 nucleotides), the nucleocapsid.
"Many of these Bunyaviridae, the so-called emerging infections," said molecular virologist Richard Elliott, at the University of Glasgow, Scotland, "are recognized as posing an increasing threat to human health."
At Yale University School of Medicine, New Haven, Conn., molecular virologist John Rose warned that negative-stranded RNA viruses include "some of the most serious and notorious pathogens, of great medical and economic importance."
Elliott is senior author of an article in a recent Proceedings of the National Academy of Sciences (PNAS), dated Dec. 24, 1996. Its title: "Rescue of a segmented negative-strand RNA virus entirely from cloned complementary DNAs."
Rose, who wrote an accompanying commentary to that paper, told BioWorld Today: "Their work is the first case of a segmented virus, where you can get the whole virus back from DNA copies of the genomic segments. So you can manipulate any gene in that virus now, and get live virus back that's viable. It's really a step beyond what's been done with other segmented, negative-stranded viruses."
The Yale researcher explained: "Now you can use all the tools of genetic engineering based on DNA for an RNA virus. If you can manipulate only at the RNA level, you're very limited. Limited in doing any sort of genetic manipulation — site-directed mutagenesis, looking at protein functions and domains, viral assembly. And you can make directed attenuated, avirulent, viral mutations for vaccine production."
Rose concluded: "Now that we have direct access to these negative-strand genomes, the applications seem absolutely limitless." *