The US 9, 10, 11, and 12 Genes of Herpes Simplex Virus Type 1 Are of No Importance for Its Neurovirulence and Latency in Mice

Nishiyama, Yukihiro; Kurachi, Ryo; Daikoku, Tohru; Umene, Kenichi

doi:10.1006/viro.1993.1279

Cited by 49 publications

(45 citation statements)

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“…Further work, however, is necessary to understand these results, as gE and gI null viruses are markedly attenuated in this model. It is noteworthy that a similar differential expression of virulence was observed with an HSV-1 mutant lacking Us9, Us10, Us11, and Us12 following peripheral or central infection (32).…”

Section: Discussionsupporting

confidence: 58%

“…While the phenotypes of individual null mutants of gE, gI, and Us2 have been analyzed, the phenotype of a PRV Us9 null virus in an otherwise wildtype background has never been reported. All previously char-acterized Us9 mutant viruses contained additional mutations, especially in the neighboring genes, the gI and gE genes (30,32,(35)(36)(37)43). Therefore, to determine the Us9 null phenotype in vitro and in vivo, we constructed two isogenic strains of PRV Becker containing defined mutations in the Us9 gene.…”

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confidence: 99%

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Role of Pseudorabies Virus Us9, a Type II Membrane Protein, in Infection of Tissue Culture Cells and the Rat Nervous System

Brideau

Card

Enquist

2000

J Virol

112

169

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The protein product of the pseudorabies virus (PRV) Us9 gene is a phosphorylated, type II membrane protein that is inserted into virion envelopes and accumulates in the trans-Golgi network. It is among a linked group of three envelope protein genes in the unique short region of the PRV genome which are absent from the attenuated Bartha strain. We found that two different Us9 null mutants exhibited no obvious phenotype after infection of PK15 cells in culture. Unlike those of gE and gI null mutants, the plaque size of Us9 null mutants on Madin-Darby bovine kidney cells was indistinguishable from that of wild-type virus. However, both of the Us9 null mutants exhibited a defect in anterograde spread in the visual and cortical circuitry of the rat. The visual system defect was characterized by restricted infection of a functionally distinct subset of visual projections involved in the temporal organization of behavior, whereas decreased anterograde spread of virus to the cortical projection targets was characteristic of animals receiving direct injections of virus into the cortex. Spread of virus through retrograde pathways in the brain was not compromised by a Us9 deletion. The virulence of the Us9 null mutants, as measured by time to death and appearance of symptoms of infection, also was reduced after their injection into the eye, but not after cortical injection. Through sequence analysis, construction of revertants, measurement of gE and gI protein synthesis in the Us9 null mutants, and mixedinfection studies of rats, we conclude that the restricted-spread phenotype after infection of the rat nervous system reflects the loss of Us9 and is not an indirect effect of the Us9 mutations on expression of glycoproteins gE and gI. Therefore, at least three viral envelope proteins, Us9, gE, and gI, function together to promote efficient anterograde transneuronal infection by PRV in the rat central nervous system.Pseudorabies virus (PRV) is a neurotropic alphaherpesvirus of the Herpesviridae family that is able to infect neurons of both the peripheral and central nervous systems of a wide variety of mammals and birds (4, 39). When PRV replicates and spreads in the nervous system, it acts as a self-amplifying tracer of synaptically connected neurons (10, 16). Integral to this process is the demonstrated ability of the virus to exploit the polarized cellular architecture of neurons and move throughout the brain of a host organism. Thus, assays of the spread of virus through the brain naturally incorporate a determination of the direction of viral transport through a circuit. Direction in the nervous system is defined by the terms "anterograde" and "retrograde," which can be used to describe directional movement of virus inside a cell as well as the spread of virus between synaptically connected neurons. We use the terms anterograde spread and retrograde spread in this report to describe movement of virus between synaptically connected neurons. Spread from the primary infected neuron to the second-order uninfected neuron in...

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Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

Role of Pseudorabies Virus Us9, a Type II Membrane Protein, in Infection of Tissue Culture Cells and the Rat Nervous System

Brideau

Card

Enquist

2000

J Virol

112

169

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“…The US3 protein kinase of HSV-1 has been shown to be involved in the phosphorylation of the essential UL34 gene product, but phosphorylation is not essential for the replication of HSV-1 in Vero or baby hamster kidney cells (Purves et al, 1991;Purves & Roizman, 1992). Our recent studies have shown that L1BR1, unlike wild-type HSV-2, cannot grow in peritoneal macrophages of mice (Nishiyama et al, 1992;Kurachi et al, 1993) or in macrophage-like cell lines such as RAW264 and U-937 (data not shown). The phosphorylation of the target proteins by US3 protein kinase might be indispensable for virus replication in selected cells.…”

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confidence: 95%

“…Although the US3-disrupted mutant (L1BR1) grew as efficiently as the parent virus in Vero cells and mouse embryo fibroblasts, the mutant was more than 10000-fold less virulent than the parent virus following intraperitoneal and footpad infection in mice, and failed to grow in peritoneal macrophages (Nishiyama et al, 1992;Kurachi et al, 1993). The biochemical properties of the HSV-2 US3 protein kinase were similar to those of the HSV-1 counterpart and the pseudorabies virus-encoded 38K protein kinase Katan et al, 1985;Purves et al, 1987), but were different in several other respects .…”

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confidence: 99%

Identification of a target protein of US3 protein kinase of herpes simplex virus type 2

Daikoku

Kurachi²,

Tsurumi³

et al. 1994

Journal of General Virology

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Herpes simplex virus type 2 (HSV-2) gene US3 has been shown to encode a serine-threonine protein kinase. In this study, we have tried to identify target proteins of the US3 protein kinase using a US3 lacZ insertion mutant of HSV-2. When permeabilized cells were labelled with [~-32p]ATP under the optimum conditions for the US3 enzyme, the most striking difference between wild-type HSV-2 strain 186-and mutant-infected cells was observed in the phosphorylation of proteins ranging in M r values from 14K to 22K. Studies of in vitro phosphorylation with purified virions and with cells infected with a US9-defective HSV-1 mutant suggested that a tegment phosphoprotein encoded by the US9 gene may be a target of HSV-2 US3 protein kinase.

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“…As opposed to HSV-1 strains which lack ICP34.5, US11-null viruses grow normally in vitro and are slightly attenuated in vivo. [24][25][26] These small phenotypes may be due to compensation by the dominant effect of extant ICP34.5. We have therefore generated an HSV-1 double mutant that is unable to bind Beclin 1 and lacks US11and are determining whether US11 contributes to control of xenophagy.…”

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confidence: 99%

Xenophagy in herpes simplex virus replication and pathogenesis

Alexander

Leib²

2008

Autophagy

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The US 9, 10, 11, and 12 Genes of Herpes Simplex Virus Type 1 Are of No Importance for Its Neurovirulence and Latency in Mice

Cited by 49 publications

References 0 publications

Role of Pseudorabies Virus Us9, a Type II Membrane Protein, in Infection of Tissue Culture Cells and the Rat Nervous System

Role of Pseudorabies Virus Us9, a Type II Membrane Protein, in Infection of Tissue Culture Cells and the Rat Nervous System

Identification of a target protein of US3 protein kinase of herpes simplex virus type 2

Xenophagy in herpes simplex virus replication and pathogenesis

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