Biological properties of herpes simplex virus 2 replication-defective mutant strains in a murine nasal infection model.
We used a mouse nasal model of herpes simplex virus 2 (HSV-2) infection to examine the biological properties of HSV-2 wild-type (wt), TK-negative, and replication-defective strains in vivo. Nasal septa tissue is the major site of wt viral replication post intranasal (i.n.) inoculation. The HSV-2 strain 186 syn(+)-1 wt virus caused lethal encephalitis at doses of 10(4) PFU and above per nostril, and at lower doses no neurons in the trigeminal ganglia were positive for the latency-associated transcript, indicating a lack of latent infection. The 186DeltaKpn TK-negative mutant virus replicated in nasal septa tissue but showed low-level replication in trigeminal ganglia at only one timepoint. In situ hybridization of trigeminal ganglia showed that the number of LAT-positive neurons was proportional to the inoculum dose from 10(3) to 10(6) PFU per nare. The replication-defective mutant virus 5BlacZ showed no replication in nasal septa tissue and no persistence of viral DNA at the inoculation site or the trigeminal ganglia. Nevertheless, inoculation of 5BlacZ or the double-mutant dl5-29 at distal sites reduced acute replication and latent infection of 186DeltaKpn following intranasal challenge. This infection model provides a biological system to test the properties of HSV-2 strains and shows that replication-defective mutant strains do not persist at sites of inoculation or in sensory ganglia but can induce immune protection that reduces the latent viral load of a challenge virus.
Jones
C A
CA
Department of Microbiology and Molecular Genetics, Children's Hospital, Boston, Massachusetts 02115, USA.
Taylor
T J
TJ
Knipe
D M
DM
D000818:Animals; D004279:DNA, Viral / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000276:immunology / Q000821:virology*; D005260:Female; D017950:Ganglia, Sensory / Q000821:virology; D018258:Herpesvirus 2, Human / Q000201:enzymology / Q000235:genetics; D007114:Immunization; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009297:Nasal Mucosa / Q000821:virology; D016133:Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D017735:Virus Latency; D014779:Virus Replication / Q000235:genetics
D004279:DNA, Viral; D013937:Thymidine Kinase