A HERPES-SIMPLEX VIRUS TYPE-1 MUTANT WITH A DELETION IMMEDIATELY UPSTREAM OF THE LAT LOCUS ESTABLISHES LATENCY AND REACTIVATES FROM LATENTLY INFECTED MICE WITH NORMAL KINETICS
J. Maggioncalda et al., A HERPES-SIMPLEX VIRUS TYPE-1 MUTANT WITH A DELETION IMMEDIATELY UPSTREAM OF THE LAT LOCUS ESTABLISHES LATENCY AND REACTIVATES FROM LATENTLY INFECTED MICE WITH NORMAL KINETICS, Journal of neurovirology, 2(4), 1996, pp. 268-278
The latency associated transcripts (LATs) are the only abundant viral
gene products detected during latent herpes simplex virus (HSV) infect
ion of peripheral nerves in animals and people. A LAT promoter has bee
n identified and mutant viruses with lesions removing the promoter and
surrounding region have been observed to reactivate slowly from trige
minal ganglia (TG) explanted from latently infected mice. Previous wor
k has shown that most mutants with lesions limited to regions downstre
am of the LAT promoter reactivate normally. Therefore, to help map the
boundaries of the slow reactivation phenotype, a mutant virus with le
sions located immediately upstream of the LAT promoter was constructed
and called 17 Delta S/N. 17 Delta S/N contains a 437 nucleotide (nt)
deletion 332 nts upstream of the TATAA box of the LAT promoter, In pro
ductively infected cells, 17 Delta S/N failed to synthesize detectable
amounts of the 1.1 and 1.8 kb transcripts which are produced during w
ild-tgpe infections and are specified by a region just upstream of the
LAT promoter, However, 17 Delta S/N did produce normal amounts of LAT
in tissue culture as well as ill neurons derived from latently infect
ed cells, as ascertained by Northern blot and in situ hybridization an
alysis. Moreover, in latently infected mice, 17 Delta S/N established
and maintained infection in as many neurons as did wild type virus, as
determined by in situ polymerase chain reaction (PCR) to deject viral
DNA. Final ly, the virus reactivated from TG derived from latently in
fected mice with kinetics indistinguishable from those of wild-type vi
rus, Therefore, reactivation from latency, in this model system, does
not appear to require function from the viral genomic region located i
mmediately upstream of the LAT promoter.