Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice

Sears, Amy E.; Halliburton, I. W.; Meignier, Bernard; Silver, Sandra; Roizman, Bernard

doi:10.1128/jvi.55.2.338-346.1985

Cited by 231 publications

(108 citation statements)

References 39 publications

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“…During productive infection, the expression of herpes simplex virus type 1 (HSV-1) genes is regulated by four virusencoded nuclear-phosphoproteins, ICPs 0, 4, 22, and 27 (2,8,12,22,24,46,56,57,61,63,64,66,68,71). The genes for these proteins, termed immediate-early genes, are the first of over 70 viral genes to be expressed in virus-infected cells.…”

mentioning

confidence: 99%

An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1

Yao

Schaffer

1995

J Virol

164

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Among the five immediate-early regulatory proteins of herpes simplex virus (HSV) type 1, only ICP0 is capable of activating all kinetic classes of viral genes. Consistent with its broad transactivating activity, ICP0 plays a major role in enhancing the reactivation of HSV from latency both in vivo and in vitro. Although not essential for viral replication, ICP0 confers a significant growth advantage on the virus, especially at low multiplicities of infection. In this report we describe the expression of a novel activity by the osteosarcoma cell line U2OS that can substitute functionally for ICP0. Compared with Vero cells, both U2OS cells and cells of the ICP0-expressing line 0-28 significantly enhanced the plating efficiency of an ICP0 null mutant, 7134. In contrast, the plating efficiencies of the wild-type virus in all three cell types were similar. Single-step growth experiments demonstrated that the yield of 7134 in U2OS cells was severalfold higher than that in 0-28 cells and about 100-fold higher than that in Vero cells. In order to identify the viral genes whose expression is enhanced by the activity in U2OS cells, levels of expression of selected viral proteins in extracts of Vero and U2OS cells were compared by Western blot (immunoblot) analysis following low-multiplicity infection. At a multiplicity of 0.1 PFU per cell, the levels of expression of the immediate-early protein ICP4 and the early protein gD in 7134-infected U2OS cells were significantly higher than those in 7134-infected Vero cells. When infections were carried out at a multiplicity of 1 PFU per cell, however, no major differences in the levels of expression of these proteins in U2OS and Vero cells were observed. Cycloheximide reversal experiments demonstrated that the cellular activity expressed in U2OS cells that promotes high-level expression of ICP4 is not synthesized de novo but appears to exist as a preformed protein(s). To confirm this observation and to determine whether, like immediate-early genes, early, delayed-early, and late viral genes are also responsive to the cellular activity, transient-expression assays were performed. The results of these tests demonstrated that basal levels of expression from immediate-early, early, and delayed-early promoters, but not that from a late promoter, were significantly higher in U2OS cells than in Vero cells and that this enhancement occurred in the absence of viral proteins. Mutational analysis of the ICP4 promoter, the most responsive of the HSV type 1 promoters tested, has shown that the 139-bp sequence between the SphI and SacII sites is required for the high basal level of expression of ICP4 in U2OS cells.

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confidence: 99%

An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1

Yao

Schaffer

1995

J Virol

164

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“…The fcr-1 gene is nonessential for replication in cell culture and has no phenotype in vitro. Herpesvirus functions have been shown to modulate virus-host interactions such as antigen presentation and immune system control (2,4,12,15,17,31,34,37,(39)(40)(41), tissue tropism (3-5, 23, 27), virus spread (9,25,42), and the establishment of latency (33). Most of these functions are encoded by nonessential genes.…”

Section: Discussionmentioning

confidence: 99%

Virus Attenuation after Deletion of the Cytomegalovirus Fc Receptor Gene Is Not due to Antibody Control

Crnković-Mertens

Messerle

Milotic

et al. 1998

J Virol

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The murine cytomegalovirus (MCMV) fcr-1 gene codes for a glycoprotein located at the surface of infected cells which strongly binds the Fc fragment of murine immunoglobulin G. To determine the biological significance of the fcr-1 gene during viral infection, we constructed MCMV fcr-1 deletion mutants and revertants. The fcr-1 gene was disrupted by insertion of the Escherichia coli lacZ gene. In another mutant, the marker gene was also deleted, by recombinase cre. As expected for its hypothetical role in immunoevasion, the infection of mice with fcr-1 deletion mutants resulted in significantly restricted replication in comparison with wild-type MCMV and revertant virus. In mutant mice lacking antibodies, however, the fcr-1 deletion mutants also replicated poorly. This demonstrated that the cell surface-expressed viral glycoprotein with FcR activity strongly modulates the virus-host interaction but that this biological function is not caused by the immunoglobulin binding property.

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“…In addition to interacting with the host protein quality control machinery, ICP22 plays several other roles in HSV infection. It is necessary for efficient viral replication and latency in mouse and guinea pig infection models and is required for viral growth in cell culture in most but not all cell types (31,32,67,71). ICP22 has been implicated in a wide-range of processes including gene expression, cell cycle control, viral assembly and nuclear egress (35,40,72,73).…”

Section: Roles Of Icp22 In Hsv Infectionmentioning

confidence: 99%

“…The HSV-1 immediate early protein ICP22 plays several seemingly diverse roles in the virus life cycle and is essential in most but not all cell lines (31,32). ICP22 is essential for the recruitment of Hsc70 into VICE domains in HSV-infected cells (33).…”

Section: Introductionmentioning

confidence: 99%

“…ICP22 is essential for the recruitment of Hsc70 into VICE domains in HSV-infected cells (33). In addition to its ability to influence the host protein quality control machinery (6,33), ICP22 is required for late viral gene expression in non-permissive cell lines (31,32,34), modification of RNA pol II (35)(36)(37)(38)(39) and cell cycle regulation (40)(41)(42). In this paper, we test the hypothesis that ICP22 plays a chaperone-like function during HSV-1 infection.…”

Section: Introductionmentioning

confidence: 99%

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The HSV-1 immediate early protein ICP22 is a J-like protein required for Hsc70 reorganization during lytic infection

Adlakha

Bezsonova

et al. 2019

Preprint

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Word count 243 Total Word Count: 5,765ABSTRACT Molecular chaperones and co-chaperones are the most abundant cellular effectors of protein homeostasis, assisting protein folding and preventing aggregation of misfolded proteins. We have previously shown that HSV-1 infection results in the drastic spatial reorganization of the cellular chaperone Hsc70 into nuclear domains called VICE (Virus Induced Chaperone Enriched) domains and that this recruitment is dependent on the viral immediate early protein ICP22. In this paper, we present several lines of evidence supporting the notion that ICP22 functions as a virally encoded co-chaperone (J-protein/Hsp40) functioning together with its Hsc70 partner to recognize and manage aggregated and misfolded proteins. We show that ICP22 results in (i) nuclear sequestration of non-native proteins, (ii) reduction of cytoplasmic aggresomes in cells expressing aggregation-prone proteins and (iii) thermoprotection against heat-inactivation of firefly luciferase.(iv) Sequence homology analysis indicated that ICP22 contains an N-terminal J-domain and a Cterminal substrate binding domain, similar to type II cellular J-proteins. ICP22 may, thus, be functionally similar to J-protein/Hsp40 co-chaperones that function together with their HSP70 partners to prevent aggregation of non-native proteins. This is not the first example of a virus hijacking a function of a cellular chaperone, as SV40 T Antigen was previously shown to contain a J-domain; however, this the first known example of the acquisition of a complete J-like protein by a virus and suggests that HSV has taken advantage of the adaptable nature of J-proteins to evolve a multi-functional co-chaperone that functions with Hsc70 to promote lytic infection.

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Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice

Cited by 231 publications

References 39 publications

An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1

An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1

Virus Attenuation after Deletion of the Cytomegalovirus Fc Receptor Gene Is Not due to Antibody Control

The HSV-1 immediate early protein ICP22 is a J-like protein required for Hsc70 reorganization during lytic infection

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