A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Journal of Virology; (USA)

OSTI ID:7194736

Heilbronn, R; zur Hausen, H ^[1]

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1. Deutsches Krebsforschungszentrum, Heidelberg (West Germany)

Herpes simplex virus (HSV) induces DNA amplification of target genes within the host cell chromosome. To characterize the HSV genes that mediate the amplification effect, combinations of cloned DNA fragments covering the entire HSV genome were transiently transfected into simian virus 40 (SV40)-transformed hamster cells. This led to amplification of the integrated SV40 DNA sequences to a degree comparable to that observed after transfection of intact virion DNA. Transfection of combinations of subclones and of human cytomegalovirus immediate-early promoter-driven expression constructs for individual open reading frames led to the identification of sic HSV genes which together were necessary and sufficient for the induction of DNA amplification: UL30 (DNA polymerase), UL29 (major DNA-binding protein), UL5, UL8, UL42, and UL52. All of these genes encode proteins necessary for HSV DNA replication. However, an additional gene coding for an HSV origin-binding protein (UL9) was required for origin-dependent HSV DNA replication but was dispensable for SV40 DNA amplification. The results show that a subset of HSV replication genes is sufficient for the induction of DNA amplification. This opens the possibility that HSV expresses functions sufficient for DNA amplification but separate from those responsible for lytic viral growth. HSV infection may thereby induce DNA amplification within the host cell genome without killing the host by lytic viral growth. This may lead to persistence of a cell with a new genetic phenotype, which would have implications for the pathogenicity of the virus in vivo.

• OSTI ID: 7194736
• Journal Information: Journal of Virology; (USA), Vol. 63:9; ISSN 0022-538X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HETEROCHROMOSOMES
GENE AMPLIFICATION
VIRAL DISEASES
PATHOGENESIS
VIRUSES
DNA-CLONING
DNA POLYMERASES
GENES
HAMSTERS
HERPES SIMPLEX
MAN
ANIMALS
CHROMOSOMES
CLONING
DISEASES
DNA HYBRIDIZATION
ENZYMES
HYBRIDIZATION
INFECTIOUS DISEASES
MAMMALS
MICROORGANISMS
NUCLEOTIDYLTRANSFERASES
PARASITES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PRIMATES
RODENTS
SKIN DISEASES
TRANSFERASES
VERTEBRATES
550700* - Microbiology