The Polyserine Tract of Herpes Simplex Virus ICP4 Is Required for Normal Viral Gene Expression and Growth in Murine Trigeminal Ganglia

AUTOR(ES)

Bates, Patricia A.

FONTE

American Society for Microbiology

RESUMO

ICP4 of herpes simplex virus (HSV) is essential for productive infection due to its central role in the regulation of HSV transcription. This study identified a region of ICP4 that is not required for viral growth in culture or at the periphery of experimentally inoculated mice but is critical for productive growth in the trigeminal ganglia. This region of ICP4 encompasses amino acids 184 to 198 and contains 13 nearly contiguous serine residues that are highly conserved among the alphaherpesviruses. A mutant in which this region is deleted (ΔSER) was able to grow on the corneas of mice and be transported back to the trigeminal ganglia. ΔSER did not grow in the trigeminal ganglia but did express low levels of several immediate-early (ICP4 and ICP27) and early (thymidine kinase [tk] and UL42) genes. It expressed very low levels of the late gC gene and did not appear to replicate DNA. This pattern of gene expression was similar to that observed for a tk mutant, dlsptk. Both ΔSER and dlsptk expressed higher levels of the latency-associated transcript (LAT) per genome earlier in infected ganglia than did the wild-type virus, KOS. However, infected ganglia from all three viruses accumulated the same level of LAT per genome at 30 days postinfection (during latency). The data suggest that the polyserine tract of ICP4 provides an activity that is required for lytic infection in ganglia to progress to viral DNA synthesis and full lytic gene expression. In the absence of this activity, higher levels of LAT per genome accumulate earlier in infection than with wild-type virus.

Documentos Relacionados

• The Transgenic ICP4 Promoter Is Activated in Schwann Cells in Trigeminal Ganglia of Mice Latently Infected with Herpes Simplex Virus Type 1
• Temperature-sensitive mutants in herpes simplex virus type 1 ICP4 permissive for early gene expression.
• Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia.
• Association of herpes simplex virus regulatory protein ICP4 with sequences spanning the ICP4 gene transcription initiation site.
• Herpes simplex virus transactivator ICP4 operationally substitutes for the cellular transcription factor Sp1 for efficient expression of the viral thymidine kinase gene.