scholarly journals VP22 of Herpes Simplex Virus 1 Promotes Protein Synthesis at Late Times in Infection and Accumulation of a Subset of Viral mRNAs at Early Times in Infection

2008 ◽  
Vol 83 (2) ◽  
pp. 1009-1017 ◽  
Author(s):  
Carol Duffy ◽  
Ekaette F. Mbong ◽  
Joel D. Baines
Keyword(s):  
Protein Synthesis ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Proteins ◽  
Immediate Early ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Viral Mrnas ◽  
Early Protein ◽  
Simplex Virus

ABSTRACT VP22, encoded by the UL49 gene, is one of the most abundant proteins of the herpes simplex virus 1 (HSV-1) tegument. In the present study we show VP22 is required for optimal protein synthesis at late times in infection. Specifically, in the absence of VP22, viral proteins accumulated to wild-type levels until ∼6 h postinfection. At that time, ongoing synthesis of most viral proteins dramatically decreased in the absence of VP22, whereas protein stability was not affected. Of the individual proteins we assayed, VP22 was required for optimal synthesis of the late viral proteins gE and gD and the immediate-early protein ICP0 but did not have discernible effects on accumulation of the immediate-early proteins ICP4 or ICP27. In addition, we found VP22 is required for the accumulation of a subset of mRNAs to wild-type levels at early, but not late, times in infection. Specifically, the presence of VP22 enhanced the accumulation of gE and gD mRNAs until ∼9 h postinfection, but it had no discernible effect at later times in infection. Also, VP22 did not significantly affect ICP0 mRNA at any time in infection. Thus, the protein synthesis and mRNA phenotypes observed with the UL49-null virus are separable with regard to both timing during infection and the genes affected and suggest separate roles for VP22 in enhancing the accumulation of viral proteins and mRNAs. Finally, we show that VP22's effects on protein synthesis and mRNA accumulation occur independently of mutations in genes encoding the VP22-interacting partners VP16 and vhs.

scholarly journals Role of Herpes Simplex Virus 1 Immediate Early Protein ICP22 in Viral Nuclear Egress

2014 ◽  
Vol 88 (13) ◽  
pp. 7445-7454 ◽  
Author(s):  
Y. Maruzuru ◽  
K. Shindo ◽  
Z. Liu ◽  
M. Oyama ◽  
H. Kozuka-Hata ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immediate Early ◽  
Herpes Simplex Virus 1 ◽  
Nuclear Egress ◽  
Early Protein ◽  
Simplex Virus

scholarly journals Analysis of the cellular localization of herpes simplex virus 1 immediate-early protein ICP22

2010 ◽  
Vol 25 (3) ◽  
pp. 158-167 ◽  
Author(s):  
Wei Cun ◽  
Jie Chen ◽  
Ying Zhang ◽  
Long-ding Liu ◽  
Qi-han Li
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cellular Localization ◽  
Immediate Early ◽  
Herpes Simplex Virus 1 ◽  
Early Protein ◽  
Simplex Virus

scholarly journals The Herpes Simplex Virus 1 Immediate Early Protein ICP22 Is a Functional Mimic of a Cellular J Protein

2019 ◽  
Vol 94 (4) ◽  
Author(s):  
Mitali Adlakha ◽  
Christine M. Livingston ◽  
Irina Bezsonova ◽  
Sandra K. Weller
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immediate Early ◽  
Herpes Simplex Virus 1 ◽  
Early Protein ◽  
J Proteins ◽  
J Domain ◽  
Nuclear Domains ◽  
Simplex Virus ◽  
J Protein

ABSTRACT Molecular chaperones and cochaperones are the most abundant cellular effectors of protein homeostasis, assisting protein folding and preventing aggregation of misfolded proteins. We have previously shown that herpes simplex virus 1 (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. Here, we present several lines of evidence supporting the notion that ICP22 functions as a virally encoded cochaperone (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 nonnative proteins, (ii) reduction of cytoplasmic aggresomes in cells expressing aggregation-prone proteins, and (iii) thermoprotection against heat inactivation of firefly luciferase, and (iv) sequence homology analysis indicated that ICP22 contains an N-terminal J domain and a C-terminal substrate binding domain, similar to type II cellular J proteins. ICP22 may thus be functionally similar to J-protein/Hsp40 cochaperones that function together with their HSP70 partners to prevent aggregation of nonnative proteins. This is not the first example of a virus hijacking a function of a cellular chaperone, since simian immunodeficiency virus T antigen was previously shown to contain a J domain; however, this the first known example of the acquisition of a functional J-like protein by a virus and suggests that HSV has taken advantage of the adaptable nature of J proteins to evolve a multifunctional cochaperone that functions with Hsc70 to promote lytic infection. IMPORTANCE Viruses have evolved a variety of strategies to succeed in a hostile environment. The herpes simplex virus 1 (HSV-1) immediate early protein ICP22 plays several roles in the virus life cycle, including downregulation of cellular gene expression, upregulation of late viral gene expression, inhibition of apoptosis, prevention of aggregation of nonnative proteins, and the recruitment of a cellular heat shock protein, Hsc70, to nuclear domains. We present evidence that ICP22 functionally resembles a cellular J-protein/HSP40 family cochaperone, interacting specifically with Hsc70. We suggest that HSV has taken advantage of the adaptable nature of J proteins to evolve a multifunctional cochaperone that functions with Hsc70 to promote lytic infection.

scholarly journals Promyelocytic Leukemia Protein Mediates Interferon-Based Anti-Herpes Simplex Virus 1 Effects

2003 ◽  
Vol 77 (12) ◽  
pp. 7101-7105 ◽  
Author(s):  
Ana V. Chee ◽  
Pascal Lopez ◽  
Pier Paolo Pandolfi ◽  
Bernard Roizman
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Proteins ◽  
Promyelocytic Leukemia ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Promyelocytic Leukemia Protein ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) 1 disaggregates the nuclear domain 10 (ND10) nuclear structures and disperses its organizing promyelocytic leukemia protein (PML). An earlier report showed that ectopic overexpression of PML precludes the disaggregation of ND10 but has no effect on viral replication. PML has been reported to mediate the effects of interferon (IFN) and viral mutants lacking ICP0 (Δα0 mutants). To test the hypothesis that HSV disaggregates ND10 structures and disperses PML to preclude IFN-mediated antiviral effects, we tested the accumulation of viral proteins and virus yields from murine PML+/+ and PML−/− cells mock treated or exposed to IFN-α, IFN-γ, or both and infected with the wild-type or Δα0 mutant virus. We report the following results. (i) The levels of growth of wild-type and mutant viruses and of accumulation of viral proteins were not significantly different in untreated PML+/+ and PML−/− cells. (ii) Major effects of IFN-α and -γ were observed in PML+/+ cells infected with the Δα0 mutant virus, and more minor effects were observed in cells infected with the wild-type virus. The effects of the IFNs on either wild-type or the mutant virus in PML−/− cells were minimal. (iii) The mixture of IFN-α and -γ was more effective than either IFN alone, but again, the effect was more drastic in PML+/+ cells than in PML−/− cells. We concluded that the anti-HSV state induced by exogenous IFN is mediated by PML and that the virus targets the ND10 structures and disseminates PML in order to preclude the establishment of the antiviral state induced by IFNs.

scholarly journals Herpes simplex virus type 1 immediate-early protein ICP0 diffuses out of infected rabbit corneas

2005 ◽  
Vol 86 (11) ◽  
pp. 2979-2988 ◽  
Author(s):  
Julie Naito ◽  
Kevin R. Mott ◽  
Nelson Osorio ◽  
Ling Jin ◽  
Guey-Chuen Perng
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Proteins ◽  
Immediate Early ◽  
Corneal Scarring ◽  
Early Protein ◽  
Latently Infected ◽  
Protein Icp0 ◽  
Simplex Virus ◽  
Hsv 1

Herpes stromal keratitis (HSK) results from infection of herpes simplex virus (HSV) in the cornea. Recurrent HSV infection is a leading cause of corneal scarring and visual loss. Although it is generally thought that HSK is the result of an immune response to one or more viral proteins, no viral proteins have been detected in HSK corneas. Thus, the viral proteins involved in HSK, if any, remain undetermined. In contrast, it is reported here that when HSK corneal buttons from latently infected rabbits were fixed using standard procedures, the important immediate-early HSV-1 protein ICP0 was readily detected in the fixative by Western blotting. Similarly, when HSK corneal buttons were soaked in buffer (rather than fixative), ICP0 was readily detected in the soaking buffer. Other HSV-1 proteins were not detected either in the fixative or in the soaking buffer. It is also reported here that ICP0 was consistently detected in virus-free tears from the eyes of rabbits acutely infected with HSV-1. These results suggest that ICP0 rapidly diffuses out of the cornea and may explain why ICP0 was detected in the fixative of HSK corneas and in the soaking buffer of acutely infected corneas.

scholarly journals Herpes Simplex Virus 1 UL34 Protein Regulates the Global Architecture of the Endoplasmic Reticulum in Infected Cells

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Fumio Maeda ◽  
Jun Arii ◽  
Yoshitaka Hirohata ◽  
Yuhei Maruzuru ◽  
Naoto Koyanagi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Null Mutation ◽  
Wild Type ◽  
Herpes Simplex Virus 1 ◽  
Nuclear Egress ◽  
Infected Cells ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Upon herpes simplex virus 1 (HSV-1) infection, the CD98 heavy chain (CD98hc) is redistributed around the nuclear membrane (NM), where it promotes viral de-envelopment during the nuclear egress of nucleocapsids. In this study, we attempted to identify the factor(s) involved in CD98hc accumulation and demonstrated the following: (i) the null mutation of HSV-1 UL34 caused specific dispersion throughout the cytoplasm of CD98hc and the HSV-1 de-envelopment regulators, glycoproteins B and H (gB and gH); (ii) as observed with CD98hc, gB, and gH, wild-type HSV-1 infection caused redistribution of the endoplasmic reticulum (ER) markers calnexin and ERp57 around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of these markers; (iii) the ER markers colocalized efficiently with CD98hc, gB, and gH in the presence and absence of UL34 in HSV-1-infected cells; (iv) at the ultrastructural level, wild-type HSV-1 infection caused ER compression around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of the ER; and (v) the UL34-null mutation significantly decreased the colocalization efficiency of lamin protein markers of the NM with CD98hc and gB. Collectively, these results indicate that HSV-1 infection causes redistribution of the ER around the NM, with resulting accumulation of ER-associated CD98hc, gB, and gH around the NM and that UL34 is required for ER redistribution, as well as for efficient recruitment to the NM of the ER-associated de-envelopment factors. Our study suggests that HSV-1 induces remodeling of the global ER architecture for recruitment of regulators mediating viral nuclear egress to the NM. IMPORTANCE The ER is an important cellular organelle that exists as a complex network extending throughout the cytoplasm. Although viruses often remodel the ER to facilitate viral replication, information on the effects of herpesvirus infections on ER morphological integrity is limited. Here, we showed that HSV-1 infection led to compression of the global ER architecture around the NM, resulting in accumulation of ER-associated regulators associated with nuclear egress of HSV-1 nucleocapsids. We also identified HSV-1 UL34 as a viral factor that mediated ER remodeling. Furthermore, we demonstrated that UL34 was required for efficient targeting of these regulators to the NM. To our knowledge, this is the first report showing that a herpesvirus remodels ER global architecture. Our study also provides insight into the mechanism by which the regulators for HSV-1 nuclear egress are recruited to the NM, where this viral event occurs.

scholarly journals Herpes Simplex Virus ICP27 Is Required for Virus-Induced Stabilization of the ARE-Containing IEX-1 mRNA Encoded by the Human IER3 Gene

2006 ◽  
Vol 80 (19) ◽  
pp. 9720-9729 ◽  
Author(s):  
Jennifer A. Corcoran ◽  
Wei-Li Hsu ◽  
James R. Smiley
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mapk Pathway ◽  
Immediate Early ◽  
Productive Infection ◽  
Mrna Stabilization ◽  
Early Protein ◽  
Host Shutoff ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus (HSV) stifles cellular gene expression during productive infection of permissive cells, thereby diminishing host responses to infection. Host shutoff is achieved largely through the complementary actions of two viral proteins, ICP27 and virion host shutoff (vhs), that inhibit cellular mRNA biogenesis and trigger global mRNA decay, respectively. Although most cellular mRNAs are thus depleted, some instead increase in abundance after infection; perhaps surprisingly, some of these contain AU-rich instability elements (AREs) in their 3′-untranslated regions. ARE-containing mRNAs normally undergo rapid decay; however, their stability can increase in response to signals such as cytokines and virus infection that activate the p38/MK2 mitogen-activated protein kinase (MAPK) pathway. We and others have shown that HSV infection stabilizes the ARE mRNA encoding the stress-inducible IEX-1 mRNA, and a previous report from another laboratory has suggested vhs is responsible for this effect. However, we now report that ICP27 is essential for IEX-1 mRNA stabilization whereas vhs plays little if any role. A recent report has documented that ICP27 activates the p38 MAPK pathway, and we detected a strong correlation between this activity and stabilization of IEX-1 mRNA by using a panel of HSV type 1 (HSV-1) isolates bearing an array of previously characterized ICP27 mutations. Furthermore, IEX-1 mRNA stabilization was abrogated by the p38 inhibitor SB203580. Taken together, these data indicate that the HSV-1 immediate-early protein ICP27 alters turnover of the ARE-containing message IEX-1 by activating p38. As many ARE mRNAs encode proinflammatory cytokines or other immediate-early response proteins, some of which may limit viral replication, it will be of great interest to determine if ICP27 mediates stabilization of many or all ARE-containing mRNAs.

Sign in / Sign up

Export Citation Format

Share Document