The Herpes Simplex Virus 2 UL21 Protein Is Essential for Virus Propagation
Autor: | Susan M. Johnston, Joel D. Baines, Valerie Le Sage, Yasushi Kawaguchi, Jake D. Alter, Bruce W. Banfield, Masany Jung, Elizabeth G. Wills |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
Chromosomes
Artificial Bacterial Cytoplasm viruses Herpesvirus 2 Human Immunology Viral transformation Biology medicine.disease_cause Virus Replication Microbiology Virus Cell Line Viral Proteins Capsid Viral entry Virology Alphaherpesvirinae medicine Animals Cell Nucleus Genes Essential Microbial Viability Structure and Assembly Genetic Complementation Test Viral tegument biology.organism_classification Microscopy Electron Herpes simplex virus Viral replication Microscopy Fluorescence Insect Science Gene Deletion |
Popis: | Herpes simplex virus 2 (HSV-2) is an important human pathogen that is the major cause of genital herpes infections and a significant contributor to the epidemic spread of human immunodeficiency virus infections. The UL21 gene is conserved throughout the Alphaherpesvirinae subfamily and encodes a tegument protein that is dispensable for HSV-1 and pseudorabies virus replication in cultured cells; however, its precise functions have not been determined. To investigate the role of UL21 in the HSV-2 replicative cycle, we constructed a UL21 deletion virus (HSV-2 ΔUL21) using an HSV-2 bacterial artificial chromosome, pYEbac373. HSV-2 ΔUL21 was unable to direct the production of infectious virus in noncomplementing cells, whereas the repaired HSV-2 ΔUL21 strain grew to wild-type (WT) titers, indicating that UL21 is essential for virus propagation. Cells infected with HSV-2 ΔUL21 demonstrated a 2-h delay in the kinetics of immediate early viral gene expression. However, this delay in gene expression was not responsible for the inability of cells infected with HSV-2 ΔUL21 to produce virus insofar as late viral gene products accumulated to WT levels by 24 h postinfection (hpi). Electron and fluorescence microscopy studies indicated that DNA-containing capsids formed in the nuclei of ΔUL21-infected cells, while significantly reduced numbers of capsids were located in the cytoplasm late in infection. Taken together, these data indicate that HSV-2 UL21 has an early function that facilitates viral gene expression as well as a late essential function that promotes the egress of capsids from the nucleus. |
Databáze: | OpenAIRE |
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