The product of the Herpes simplex virus 1 UL7 gene interacts with a mitochondrial protein, adenine nucleotide translocator 2

Michiko Tanaka,Yasushi Kawaguchi,Tetsutaro Sata

doi:10.1186/1743-422x-5-125

Michiko Tanaka, Yasushi Kawaguchi + Show 1 more

Open Access

https://doi.org/10.1186/1743-422x-5-125

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Abstract

The herpes simplex virus 1 (HSV-1) UL7 gene is highly conserved among herpesviridae. Since the construction of recombinant HSV-1 with a mutation in the UL7 gene has not been reported, the involvement of HSV-1 UL7 in viral replication has been unclear. In this study, we succeeded in generating a UL7 null HSV-1 mutant virus, MT102, and characterized it. Our results were as follows. (i) In Vero cells, MT102 was replication-competent, but formed smaller plaques and yielded 10- to 100-fold fewer progeny than the wild-type virus, depending on the multiplicity of infection. (ii) Using mass spectrometry-based proteomics technology, we identified a cellular mitochondrial protein, adenine nucleotide translocator 2 (ANT2), as a UL7-interacting partner. (iii) When ANT2 was transiently expressed in COS-7 cells infected with HSV-1, ANT2 was specifically co-precipitated with UL7. (iv) Cell fractionation experiments with HSV-1-infected cells detected the UL7 protein in both the mitochondrial and cytosolic fractions, whereas ANT2 was detected only in the mitochondrial fraction. These results indicate the importance of HSV-1 UL7's involvement in viral replication and demonstrate that it interacts with ANT2 in infected cells. The potential biological significance of the interaction between UL7 and ANT2 is discussed.

Highlights

Herpes simplex virus 1 (HSV-1) has a double-stranded DNA genome of about 152 kbp, from which more than 84 open reading frame (ORF) are translated
The UL7 deletion mutant virus was able to be reconstituted by transfection of pMT102, which contains a deletion in the UL7 locus of the HSV-1 genome, into
We have constructed a null mutant virus of HSV-1 UL7, called MT102, and presented evidence that MT102 is able to replicate in Vero cells, indicating that the HSV-1 UL7 gene is dispensable in HSV-1 replication in cell culture

Summary

Introduction

Herpes simplex virus 1 (HSV-1) has a double-stranded DNA genome of about 152 kbp, from which more than 84 ORFs are translated. Since Post and Roizman first characterized recombinant viruses in which a specific HSV-1 gene was mutated by the reverse genetics system [1], this gene's roles in the viral life cycle have been extensively investigated. There remain only a handful of HSV1 genes whose roles have not been investigated using a recombinant virus with a mutated gene. Information on the function(s) of the HSV UL7 gene product in the viral life cycle is limited. The only reported experimental evidence with regard to HSV UL7 is that its gene products are present in integumentary layers of mature virions, and that the viral protein is localized predominantly in the juxtanuclear cytoplasmic domains of infected cells, it is detected transiently in the nucleus [4]

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