TY - JOUR
T1 - Neuroattenuated bunyavirus variant
T2 - Derivation, characterization, and revertant clones
AU - Endres, Michael J.
AU - Valsamakis, Alexandra
AU - Gonzalez-Scarano, Francisco
AU - Nathanson, Neal
PY - 1990
Y1 - 1990
N2 - A neuroattenuated variant bunyavirus, designated RFC/25B.5 (B.5), was selected by serial passage of a reassortant clone (RFC virus) of a California serogroup virus in BHK-21 cells, followed by plaque purification of that passaged stock. Based on its virulence index (ratio of PFU/50% lethal dose), clone B5 was over 40,000-fold less virulent than its unpassaged RFC parent after intracerebral (i.e.) inoculation into adult mice. Clone B.5 also exhibited markedly reduced neuroinvasiveness after subcutaneous injection into neonatal mice, although it retained its ability to replicate and kill suckling mice after i.e. injection. A murine neuroblastoma line (NA cells) can be used as an in vitro surrogate for the adult mouse brain, since clone B.5 replicated to at least 1,000-fold-lower titers in NA cells than did several neurovirulent California serogroup viruses. Clone B.5 replicated in BHK-21 cells at 37°C to titers similar to those achieved by other California serogroup viruses but was temperature sensitive (ts) since its replication was markedly restricted at 38.9°C. Ten ts revertant clones of B.5 virus were selected at 38.9°C, and all of them lost their ts phenotype and regained the ability to replicate to high titer in NA cells and to kill adult mice after i.e. injection. Clone B.5 is the first described California serogroup virus which is truly attenuated after i.e. inoculation, and its availability will permit genetic analysis of bunyavirus neurovirulence.
AB - A neuroattenuated variant bunyavirus, designated RFC/25B.5 (B.5), was selected by serial passage of a reassortant clone (RFC virus) of a California serogroup virus in BHK-21 cells, followed by plaque purification of that passaged stock. Based on its virulence index (ratio of PFU/50% lethal dose), clone B5 was over 40,000-fold less virulent than its unpassaged RFC parent after intracerebral (i.e.) inoculation into adult mice. Clone B.5 also exhibited markedly reduced neuroinvasiveness after subcutaneous injection into neonatal mice, although it retained its ability to replicate and kill suckling mice after i.e. injection. A murine neuroblastoma line (NA cells) can be used as an in vitro surrogate for the adult mouse brain, since clone B.5 replicated to at least 1,000-fold-lower titers in NA cells than did several neurovirulent California serogroup viruses. Clone B.5 replicated in BHK-21 cells at 37°C to titers similar to those achieved by other California serogroup viruses but was temperature sensitive (ts) since its replication was markedly restricted at 38.9°C. Ten ts revertant clones of B.5 virus were selected at 38.9°C, and all of them lost their ts phenotype and regained the ability to replicate to high titer in NA cells and to kill adult mice after i.e. injection. Clone B.5 is the first described California serogroup virus which is truly attenuated after i.e. inoculation, and its availability will permit genetic analysis of bunyavirus neurovirulence.
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M3 - Article
C2 - 2182907
AN - SCOPUS:0025272152
SN - 0022-538X
VL - 64
SP - 1927
EP - 1933
JO - Journal of virology
JF - Journal of virology
IS - 5
ER -