An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ

Balan, Preetha; Davis-Poynter, Nicholas; Bell, Susanne; Atkinson, Helen; Browne, Helena; Minson, Tony

doi:10.1099/0022-1317-75-6-1245

Cited by 229 publications

(236 citation statements)

References 34 publications

Supporting

Mentioning

213

Contrasting

Order By: Relevance

“…In some cases, error bars are too small to be seen. 25). We have not detected homology between Us5 and other known viral or cellular anti-apoptosis genes.…”

Section: Discussionmentioning

confidence: 99%

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

Jerome

Chen

Lang

et al. 2001

The Journal of Immunology

108

View full text Add to dashboard Cite

HSV-1 inhibits apoptosis of infected cells, presumably to ensure that the infected cell survives long enough to allow completion of viral replication. Because cytotoxic lymphocytes kill their targets via the induction of apoptosis, protection from apoptosis could constitute a mechanism of immune evasion for HSV. Several HSV genes are involved in the inhibition of apoptosis, including Us5, which encodes glycoprotein J (gJ). Viruses deleted for Us5 showed defects in inhibition of caspase activation after Fas ligation or UV irradiation. Transfected cells expressing the Us5 gene product gJ were protected from Fas- or UV-induced apoptosis, as measured by morphology, caspase activation, membrane permeability changes, or mitochondrial transmembrane potential. In contrast, caspase 3 activation in mitochondria-free cell lysates by granzyme (gr)B was inhibited equivalently by Us5 deletion and rescue viruses, suggesting that gJ is not required for HSV to inhibition this process. However, mitochondria-free lysates from transfected cells expressing Us5/gJ were protected from grB-induced caspase activation, suggesting that Us5/gJ is sufficient to inhibit this process. Transfected cells expressing Us5/gJ were also protected from death induced by incubation with purified grB and perforin. These findings suggest that HSV has a comprehensive set of immune evasion functions that antagonize both Fas ligand- and grB-mediated pathways of CTL-induced apoptosis. The understanding of HSV effects on killing by CTL effector mechanisms may shed light on the incomplete control of HSV infections by the immune system and may allow more rational approaches to the development of immune modulatory treatments for HSV infection.

show abstract

“…In some cases, error bars are too small to be seen. 25). We have not detected homology between Us5 and other known viral or cellular anti-apoptosis genes.…”

Section: Discussionmentioning

confidence: 99%

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

Jerome

Chen

Lang

et al. 2001

The Journal of Immunology

108

View full text Add to dashboard Cite

show abstract

“…Glycoprotein E (gE) is one of such non-essential proteins (Rebordosa et al 1996, Franco et al 2002a, Spilki et al 2004). Although it is conserved among other members of the Herpesviridae family, the role of gE in the in vitro growth characteristics may vary in function of the virus species and the host cell (Balan et al 1994). In human herpesvirus type 1 (HHV-1) and varicella-zoster virus (HHV-3), gE can be found non-covalently linked to gI, forming a Fc binding site for immunoglobulins, which has been proposed as a mechanism to protect virus-infected cells from lysis by the immune system (Olson et al 1997).…”

Section: Introductionmentioning

confidence: 99%

“…In human herpesvirus type 1 (HHV-1) and varicella-zoster virus (HHV-3), gE can be found non-covalently linked to gI, forming a Fc binding site for immunoglobulins, which has been proposed as a mechanism to protect virus-infected cells from lysis by the immune system (Olson et al 1997). The gE complex in HHV-1 and HHV-3 is also important for in vitro cell-to-cell spread (Balan et al 1994, Dingwell et al 1995. In comparison to wild type viruses, gE negative recombinants (gE -) produce smaller plaque sizes in vitro, although the growth kinetics or penetration process of the virus seem not to be dependent on the presence of gE (Rebordosa et al 1996, Chowdhury et al 1999, Spilki et al 2004 In previous studies, we described the construction of a recombinant vaccine, based on a Brazilian BoHV-1 isolate, from which the gE gene was deleted.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a gE-deleted, bovine herpesvirus 1 (BoHV-1) inactivated vaccine

Silva

Esteves²,

Dezen

et al. 2009

Pesq. Vet. Bras.

View full text Add to dashboard Cite

Pesq. Vet. Bras. 29(7): 545-551, julho 2009 RESUMO.-[Eficácia de uma vacina inativada, gE-deletada, contra o herpesvírus bovino tipo 1 (BoHV-1).] O Herpesvírus bovino tipo 1 (BoHV-1) é reconhecido como um importante agente de perdas econômicas em bovinos. Vacinação tem sido amplamente empregada para minimizar as perdas conseqüentes a infecções com o BoHV-1. Reportamos previamente o desenvolvimento de uma vacina diferencial para BoHV-1, baseada em um recombinante do qual a glicoproteína gE (gE) foi deletada (265gE -). No presente trabalho foi realizada a avaliação da eficácia de tal recombinante como vacina inativada. Cinco bovinos soronegativos para BoHV-1 foram vacinadas por via intramuscular no dia 0 e revacinadas 30 dias Bovine herpesvirus type 1 (BoHV-1) is recognized as a major cause of economic losses in cattle. Vaccination has been widely applied to minimize losses induced by BoHV-1 infections. We have previously reported the development of a differential BoHV-1 vaccine, based on a recombinant glycoprotein E (gE)-deleted virus (265gE -). In present paper the efficacy of such recombinant was evaluated as an inactivated vaccine. Five BoHV-1 seronegative calves were vaccinated intramuscularly on day 0 and boostered 30 days later with an inactivated, oil adjuvanted vaccine containing an antigenic mass equivalent to 10 7.0 fifty per cent cell culture infectious doses (CCID 50 ) of 265gE -. Three calves were kept as non vaccinated controls. On day 60 post vaccination both vaccinated and controls were challenged with the virulent parental strain. No clinical signs or adverse effects were seen after or during vaccination. After challenge, 2/5 vaccinated calves showed mild clinical signs of infection, whereas all non vaccinated controls displayed intense rhinotracheitis and shed virus for longer and to higher titres than vaccinated calves. Serological responses were detected in all vaccinated animals after the second dose of vaccine, but not on control calves. Following corticosteroid administration in attempting to induce reactivation of the latent infection, no clinical signs were observed in vaccinated calves, whereas non vaccinated controls showed clinical signs of respiratory disease. In view of its immunogenicity and protective effect upon challenge with a virulent BoHV-1, the oil adjuvanted preparation with the inactivated 265gE -recombinant was shown to be suitable for use as a vaccine.INDEX TERMS: Bovine herpesvirus type 1, BoHV-1, recombinant vaccine, inactivated vaccine.Pesq. Vet. Bras. 29 (7)

show abstract

“…The molecular mechanism of this mode of transmission is poorly understood, but it is known to share some mechanistic details with the entry of extracellular virions (1), namely the use of the essential core fusion machinery, consisting of glycoproteins B, D, H, and L (gB, gD, gH, and gL, respectively). Moreover, it requires glycoproteins E and I (gE and gI, respectively) (1), which are not necessary for "cell-free" transmission (3). Consequently, HSV mutants lacking gE/gI are severely restricted for spread to neuronal cells (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Function of glycoprotein E of herpes simplex virus requires coordinated assembly of three tegument proteins on its cytoplasmic tail

Han

Chadha

Starkey

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

140

View full text Add to dashboard Cite

Glycoprotein E (gE) of HSV plays a key role in cell-to-cell spread and virus-induced cell fusion. Here, we report that this function of gE requires the cooperation of tegument proteins UL11, UL16, and UL21. We found that the four proteins come together with very high efficiency to form a complex in transfected cells and in a manner that is regulated and coordinated. In particular, the inefficient interaction of UL16 with each membrane protein (UL11 and gE) observed in pairwise transfections became efficient when other binding partners were present. The significance of these interactions was revealed in studies of viral mutants, which showed that each of these tegument proteins is critical for processing, transport, and biological activity of gE. These findings provide insights into the mechanisms of how gE executes its function and also have implications in understanding HSV assembly and budding.

show abstract

An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ

Cited by 229 publications

References 34 publications

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

Efficacy of a gE-deleted, bovine herpesvirus 1 (BoHV-1) inactivated vaccine

Function of glycoprotein E of herpes simplex virus requires coordinated assembly of three tegument proteins on its cytoplasmic tail

Contact Info

Product

Resources

About