Abstract
The Epstein-Barr virus (EBV) lytic program includes lytic viral DNA replication and the production of a viral particle into which the replicated viral DNA is packaged. The terminal repeats (TRs) located at the end of the linear viral DNA have been identified as the packaging signals. A TR-negative (TR(-)) mutant therefore provides an appropriate tool to analyze the relationships between EBV DNA packaging and virus production. Here, we show that supernatants from lytically induced 293 cells carrying TR mutant EBV genomes (293/TR(-)) contain large amounts of viral particles devoid of viral DNA which are nevertheless able to bind to EBV target cells. This shows that viral DNA packaging is not a prerequisite for virion formation and egress. Rather surprisingly, supernatants from lytically induced 293/TR(-) cells also contained rare infectious viruses carrying the viral mutant DNA. This observation indicates that the TRs are important but not absolutely essential for virus encapsidation.
MeSH Terms
Cell Line
Defective Viruses/genetics,metabolism,pathogenicity
Genome, Viral
Herpesvirus 4, Human/genetics,metabolism,pathogenicity
Humans
Mutation
Terminal Repeat Sequences/genetics
Virion/genetics,metabolism,pathogenicity
Virus Assembly
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Feederle R
German Cancer Research Center, Department of Virus-Associated Tumours, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Shannon-Lowe C
Baldwin G
Delecluse H J
References (19)
19 references, click to expand
-
The terminase subunits pUL56 and pUL89 of human cytomegalovirus are DNA-metabolizing proteins with toroidal structure.
Nucleic Acids Res. 2002 Apr 1;30(7):1695-703
PMID: 11917032
-
CYTOLOGY OF BURKITT'S TUMOUR (AFRICAN LYMPHOMA).
Lancet. 1964 Feb 1;1(7327):238-40
PMID: 14086209
-
Relationship of herpes simplex virus genome configuration to productive and persistent infections.
Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7871-6
PMID: 12796511
-
Human papillomavirus vaccine as a new way of preventing cervical cancer: a dream or the future?
Ann Oncol. 2004 Feb;15(2):197-200
PMID: 14760108
-
Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma.
Biomedicine. 1975 Jul;22(4):276-84
PMID: 179629
-
Characteristics of a human cell line transformed by DNA from human adenovirus type 5.
J Gen Virol. 1977 Jul;36(1):59-74
PMID: 886304
-
Sequence complexity of circular Epstein-Bar virus DNA in transformed cells.
J Virol. 1981 Oct;40(1):11-9
PMID: 6270367
-
Isolation and characterization of a noninfectious virion-like particle released from cells infected with human strains of cytomegalovirus.
Virology. 1983 Oct 15;130(1):118-33
PMID: 6314643
-
Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis.
J Virol. 1984 Apr;50(1):248-54
PMID: 6321792
-
Herpes simplex virus amplicon: cleavage of concatemeric DNA is linked to packaging and involves amplification of the terminally reiterated a sequence.
J Virol. 1986 Mar;57(3):933-41
PMID: 3005637
-
The cleavage recognition signal is contained within sequences surrounding an a-a junction in herpes simplex virus DNA.
Virology. 1988 Nov;167(1):25-30
PMID: 2847414
-
Gene mapping and expression of two immunodominant Epstein-Barr virus capsid proteins.
J Virol. 1993 Jul;67(7):3908-16
PMID: 7685403
-
Structure and role of the terminal repeats of Epstein-Barr virus in processing and packaging of virion DNA.
J Virol. 1995 May;69(5):3147-55
PMID: 7707542
-
Sp1 binds to the precise locus of end processing within the terminal repeats of Epstein-Barr virus DNA.
J Virol. 1997 Aug;71(8):6136-43
PMID: 9223508
-
Chimeric papillomavirus virus-like particles elicit antitumor immunity against the E7 oncoprotein in an HPV16 tumor model.
Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1800-5
PMID: 9465097
-
The gene product of human cytomegalovirus open reading frame UL56 binds the pac motif and has specific nuclease activity.
J Virol. 1998 Mar;72(3):2259-64
PMID: 9499084
-
Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells.
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8245-50
PMID: 9653172
-
A first-generation packaging cell line for Epstein-Barr virus-derived vectors.
Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5188-93
PMID: 10220441
-
Glycoprotein gp110 of Epstein-Barr virus determines viral tropism and efficiency of infection.
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15036-41
PMID: 12409611