A mouse model for varicella-zoster virus latency.
Following primary infection with varicella-zoster virus (VZV), the virus establishes a latent infection in humans. The molecular pathogenesis of VZV latency is not well understood, mainly due to the lack of an adequate animal model. We report here that we have developed a mouse model for VZV infection that involves corneal inoculation of mice. Although infected animals showed no signs of disease, most of the animals could not eliminate the virus early after infection. By PCR, we demonstrated that at 33 days post-infection (p.i.), viral DNA was still present in more than 60% of the animals (14/21). VZV DNA was most frequently detected in the trigeminal ganglia (7/14) followed by the brain stem (10/21), kidneys (4/21), spleen (3/20), liver (2/21) and brain (1/21). By in situ hybridization, a few cells positive for VZV mRNA were detected in the trigeminal ganglia, brain stem, cerebellum and spleen of a small number of the infected animals as late as 33 days p.i. No viral proteins were detected at the site of inoculation or in any other tissue by immunostaining. Our results suggest that VZV spreads in mice by both viraemia and axonal transport and establishes a non-productive (latent) infection.
Wroblewska
Z
Z
Wistar Institute, Philadelphia, PA 19104.
Valyi-Nagy
T
T
Otte
J
J
Dillner
A
A
Jackson
A
A
Sole
D P
DP
Fraser
N W
NW
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001483:Base Sequence; D001933:Brain Stem / Q000382:microbiology; D004195:Disease Models, Animal; D005123:Eye / Q000382:microbiology; D015870:Gene Expression; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000382:microbiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000382:microbiology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013154:Spleen / Q000382:microbiology; D012668:Trigeminal Ganglion / Q000382:microbiology; D017735:Virus Latency; D014779:Virus Replication
D000956:Antigens, Viral; D012333:RNA, Messenger; D012367:RNA, Viral