Varicella-zoster virus open reading frame 21, which is expressed during latency, is essential for virus replication but dispensable for establishment of latency.
Varicella-zoster virus (VZV) open reading frame 21 (ORF21) is one of at least five VZV genes expressed in latently infected human and rodent ganglia. To determine whether ORF21 is required for latent and lytic infection, we deleted 99% of ORF21 from the viral genome. The ORF21 deletion mutant virus could be propagated only in a cell line expressing the ORF21 protein. Insertion of the herpes simplex virus type 1 (HSV-1) homolog of VZV ORF21, HSV-1 UL37, into the ORF21 deletion mutant failed to complement the mutant for growth in cell culture. Inoculation of cotton rats with the ORF21 deletion virus resulted in latent infection in numbers of animals similar to those infected after inoculation with the parental virus. The mean numbers of latent VZV genomes were similar in animals infected with parental and ORF21 deletion viruses. Transcription of ORF63, another latency-associated gene, was detected in ganglia from similar numbers of animals infected with the mutant and parental viruses. Thus, ORF21 is the first VZV gene expressed during latency that has been shown to be dispensable for the establishment of latent infection.
Xia
Dongxiang
D
Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Srinivas
Shamala
S
Sato
Hitoshi
H
Pesnicak
Lesley
L
Straus
Stephen E
SE
Cohen
Jeffrey I
JI
D001483:Base Sequence; D017931:DNA Primers; D005816:Genetic Complementation Test; D014645:Herpesvirus 3, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016366:Open Reading Frames; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D015678:Viral Structural Proteins / Q000235:genetics; D017735:Virus Latency / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*
D017931:DNA Primers; C084763:UL37 protein, Human herpesvirus 1; D015678:Viral Structural Proteins