EVIDENCE THAT FATAL HUMAN INFECTIONS WITH LA-CROSSE VIRUS MAY BE ASSOCIATED WITH A NARROW RANGE OF GENOTYPES

La Crosse (LAC) virus belongs to the California (CAL) serogroup of the genus Bunyavirus lu, family Bunyaviridae. It is considered one of the most important mosquito-borne pathogens in North America, especially in the upper Mid-West, where it is associated with encephalitis during the time of year when mosquitoes are active. Infections occur most fr equently in children and young adults and, while most cases are resolv ed after a period of intense illness, a small fraction (< 1%) are fata l. At present there have only been three isolates of LAC virus from hu mans, all made from brain tissue postmortem. The cases yielding viruse s are separated chronologically by 33 years and geographically from Mi nnesota/Wisconsin (1960, 1978) to Missouri (1993). The M RNA sequence of the first two isolates was previously reported. The present study e xtends the observations to the isolate from the 1993 case and includes several mosquito isolates as well. A comparison of the M RNAs of thes e viruses shows that for the human isolates both nucleotide sequence a nd the deduced amino-acid sequence of the encoded proteins are highly conserved, showing a maximum variation of only 0.91% and 0.69%, respec tively. This high degree of conservation over time and space leads to the hypothesis that human infections with this particular genotype of LAC virus are those most likely to have a fatal outcome. It is also sh own that a virus with this genotype could be found circulating in mosq uitoes in an area more or less intermediate between the locations of t he first and second fatal cases. (C) 1997 Elsevier Science B.V.