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Title: Divergent Evolution of Nuclear Localization Signal Sequences in Herpesvirus Terminase Subunits

Journal Article · · Journal of Biological Chemistry
 [1];  [1];  [2]
  1. Thomas Jefferson Univ., Philadelphia, PA (United States)
  2. Thomas Jefferson Univ., Philadelphia, PA (United States); National Research Council, Bari (Italy)

The tripartite terminase complex of herpesviruses assembles in the cytoplasm of infected cells and exploits the host nuclear import machinery to gain access to the nucleus, where capsid assembly and genome-packaging occur. Here we analyzed the structure and conservation of nuclear localization signal (NLS) sequences previously identified in herpes simplex virus 1 (HSV-1) large terminase and human cytomegalovirus (HCMV) small terminase. We found a monopartite NLS at the N terminus of large terminase, flanking the ATPase domain, that is conserved only in α-herpesviruses. In contrast, small terminase exposes a classical NLS at the far C terminus of its helical structure that is conserved only in two genera of the β-subfamily and absent in α- and γ-herpesviruses. In addition, we predicted a classical NLS in the third terminase subunit that is partially conserved among herpesviruses. Bioinformatic analysis revealed that both location and potency of NLSs in terminase subunits evolved more rapidly than the rest of the amino acid sequence despite the selective pressure to keep terminase gene products active and localized in the nucleus. Here, we propose that swapping NLSs among terminase subunits is a regulatory mechanism that allows different herpesviruses to regulate the kinetics of terminase nuclear import, reflecting a mechanism of virus:host adaptation.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Inst. of Health
Grant/Contract Number:
R01GM100888; P30 CA56036
OSTI ID:
1257476
Journal Information:
Journal of Biological Chemistry, Vol. 291, Issue 21; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 20 works
Citation information provided by
Web of Science

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Cited By (4)

Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons journal January 2018
Mutual Interplay between the Human Cytomegalovirus Terminase Subunits pUL51, pUL56, and pUL89 Promotes Terminase Complex Formation journal March 2017
Terminase Large Subunit Provides a New Drug Target for Herpesvirus Treatment journal March 2019
Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro journal October 2018