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Viable Influenza A Virus Built From Scratch

NEW YORK, Aug 02 (Reuters Health) -- For the first time, scientists have used reverse genetics to create influenza A virus that can infect human cells.

Influenza A virus presents a particular challenge because its genetic material consists of RNA (instead of DNA) that requires a protein produced by the virus to be infectious. Furthermore, influenza A -- containing eight segments of RNA -- is larger than other viruses produced before, according to Yoshihiro Kawaoka of the University of Wisconsin-Madison, and coworkers.

The scientists used a system they called reverse genetics to incorporate influenza A virus genetic material into human kidney cells grown in the laboratory. As the authors describe it, reverse genetics involves inserting DNA into cells that will convert the DNA into the virus's RNA and proteins, which will then assemble the material into viable virus.

The system proved highly effective, with one cell in a thousand producing infectious influenza virus particles, according to results published in the August issue of the Proceedings of the National Academy of Sciences.

Equally important for understanding how viruses reproduce themselves and for developing new vaccines, the researchers report that they successfully generated influenza A viruses into which they had introduced two different genetic mutations.

"The most intriguing application of our reverse-genetics system may lie in the rapid production of (weakened) live-virus vaccines in cases of suspected pandemics involving new... subtypes of influenza virus," Kawaoka and colleagues write.

In addition, the investigators note, the new reverse-genetics system might be employed to deliver not only other vaccines but also genes (for gene therapy) to human cells.

"The ability to manipulate the viral (genes) without technical limitations has profound implications for the study of viral life cycles and their regulation, the function of viral proteins, and the molecular mechanisms of viral (disease)," they conclude.

SOURCE: Proceedings of the National Academy of Sciences USA 1999;96:9345-9350.


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