%0 Journal Article %A MacLean, Alasdair %A Robertson, Lesley %A McKay, Elizabeth %A Brown, S. Moira %T The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency %D 1991 %J Journal of General Virology, %V 72 %N 9 %P 2305-2310 %@ 1465-2099 %R https://doi.org/10.1099/0022-1317-72-9-2305 %I Microbiology Society, %X We have demonstrated that the variant JH2604 of the herpes simplex virus type 2 (HSV-2) strain HG52 is completely avirulent in BALB/c mice following intracranial inoculation, with an LD50 of > 107 p.f.u./mouse compared to the wild-type LD50 of < 102 p.f.u./mouse. In JH2604, a 1.5 kbp deletion extends from the DR1/Ub junction of the ‘a’ sequence to 511 bp upstream of the 5′ end of IE1 in both long repeats. We have since constructed a second variant (2701) in which only 850 bp are removed from the RL. This deletion lies entirely within the sequences deleted in JH2604 and leaves intact most of a short 189 bp open reading frame (ORF) highly conserved between HSV-1 and HSV-2. Like JH2604, 2701 shows wild-type growth characteristics and is neither host range-nor temperature-restricted. This was most noteworthy in the case of mouse 3T6 cells. 2701 has an LD50 of 5×105 p.f.u./mouse on intracranial inoculation, a value intermediate between those of HG52 and JH2604. In assays for intracranial replication, JH2604 exhibits no detectable growth with a rapid decline in virus titre, 2701 shows limited growth over the first 24 to 36 h post-inoculation before the titre again declines and HG52 grows rapidly, reaching a high titre until the mice die. Taken together these results suggest that a region of the genome upstream of IE1 encodes a gene product essential for HSV replication in neurons of the central nervous system. It is highly likely that the conserved ORF is in an important region of a polypeptide essential for neurovirulence, although the upstream sequences present in 2701 but absent from JH2604 must also play a role. Although JH2604 and 2701 are avirulent, they both establish latent infection in the dorsal root ganglia of BALB/c mice and reactivate in vitro in a manner indistinguishable from HG52. This suggests a distinct separation of the factors involved in neurovirulence and the establishment of/reactivation from latency. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-72-9-2305