Pathogenicity of glycoprotein C negative mutants of herpes simplex virus type 1 for the mouse central nervous system

Sunstrum, James; Chrisp, Clarence E.; Levine, Fred

doi:10.1016/0168-1702(88)90064-0

Cited by 23 publications

(10 citation statements)

References 49 publications

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“…Other null mutants at the gC and gJ loci have been shown to replicate normally in cell cultures (2,39,61). Therefore, any generalized replication defects in our mutants may indicate the presence of unknown secondsite mutations that could conceivably affect ICP0 promoter function.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Herpes Simplex Virus ICP0 Promoter Function in Sensory Neurons during Acute Infection, Establishment of Latency, and Reactivation In Vivo

Thompson

Shieh

Sawtell

2003

J Virol

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Despite the extensive repression of herpes simplex virus type 1 (HSV-1) gene transcription during latency, a variety of stressful stimuli can result in the reactivation of the latent genome and reentry into lytic-phase transcription (71). How the quiescent genome exits latency is not yet known. It has been suggested that ICP0 is uniquely important for the initiation of viral reactivation (reviewed in reference 19). ICP0 is a major viral transcriptional activator important for the expression of viral genes of diverse kinetic classes (8-10, 12, 60). In addition, this protein functions to promote viral mRNA translation and regulates levels of cellular proteins through interaction with the ubiquitin-proteosome pathway (18,20,45,49). These properties suggest that ICP0 can regulate both viral and host protein levels through transcriptional, translational, and posttranslational mechanisms. In a tissue culture model of latent infection, ICP0 was implicated in the efficient establishment of latency (74). ICP0-expressing adenovirus vectors that lack all other HSV genes have been shown to induce viral replication in quiescently infected tissue cultures (28,75). Further, a viral mutant lacking functional ICP0 but containing all other viral genes did not induce viral replication in similar cultures, suggesting a specific role for ICP0 (28). However, adenovirus vectors expressing ICP4 and VP16 can also induce viral replication in primary cultures derived from latently infected ganglia (26).In animal models ICP0 mutant strains can establish latent infections and can reactivate in cocultivation assays, but the levels of efficiency for both of these processes are greatly reduced compared to that seen with the wild-type strain (7,10,27,33,37). One problem with these studies is that ICP0 null mutants establish latency inefficiently, and it is therefore difficult to distinguish between the importance of this gene for establishing latency and its importance for initiating reactivation. Recently, Halford and Schaffer infected immunosuppressed mice with ICP0 null mutants in an effort to increase the establishment of latency by the null mutants. Those authors concluded (on the basis of the total amount of HSV DNA detected in ganglia by PCR and the number of explant cultures * Corresponding author. Mailing address for Richard

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Section: Resultsmentioning

confidence: 99%

Analysis of Herpes Simplex Virus ICP0 Promoter Function in Sensory Neurons during Acute Infection, Establishment of Latency, and Reactivation In Vivo

Thompson

Shieh

Sawtell

2003

J Virol

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“…Previous analyses of HSV-1 gC and gG deletion mutants during in vivo infection have failed to identify a role for either protein during viral replication in mice (7,13,14), although gC has been shown to be necessary for HSV-1 virulence in human skin implanted into severe combined immunodeficient (SCID) mice (15). gC binds the complement component C3b and protects virions and infected cells from complement mediated lysis (16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

A herpes simplex virus 1 recombinant lacking the glycoprotein G coding sequences is defective in entry through apical surfaces of polarized epithelial cells in culture and in vivo

Tran

Kissner

Westerman

et al. 2000

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

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During infection of a new host, the first surfaces encountered by herpes simplex viruses are the apical membranes of epithelial cells of mucosal surfaces. These cells are highly polarized, and the protein composition of their apical and basolateral membranes are very different, so that different viral entry pathways have evolved for each surface. To determine whether the viral glycoprotein G (gG) is specifically required for efficient infection of a particular surface of polarized cells, apical and basal surfaces were infected with wild-type virus or a gG deletion mutant. After infection of polarized cells in culture, the gG ؊ virus was deficient in infection of apical surfaces but was able to infect cells through basal membranes, replicate, and spread into surrounding cells. The gG-dependent step in apical infection was a stage beyond attachment. After in vivo infection of apical surfaces of epithelial cells of nonscarified mouse corneas, infection by glycoprotein C ؊ or gG ؊ virus was considerably reduced as compared with that observed after infection with wild-type virus. In contrast, when corneas were scarified, allowing virus access to other cell surfaces, the gG and glycoprotein C deletion mutants infected eyes as efficiently as wild-type viruses. A secondary mutation allowing infection of apical surfaces by gG ؊ virus arose readily during passage of the virus in nonpolarized cells, indicating that either the gG-dependent step of apical infection can be bypassed or that another viral protein can acquire the same function.

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“…Inactivation of the ICP34,5 gene, by deleting the gene or insertion of a stop codon inside it, generated recom- -4), protein kinase, and glycoprotein G (45). In contrast to early studies, glycoprotein C is not a virulence factor (46). It plays a role in the early stages of HSV-I replication by contributing to virus attachment to host cells, but this function is redundant with other glycoproteins and, therefore, deletion of the glycoprotein C gene does not efficiently impair virus replication and pathogenicity on intracranial injection in mice.…”

Section: And Latencymentioning

confidence: 50%

HSV and the CNS

Meyding‐Lamadé

Lamadé

1996

Neuroscientist

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Herpes simplex virus encephalitis (HSVE) is an encephalitis with a predelection for the temporal lobes and related structures that is caused by HSV-1 or HSV-2. Because HSV has many properties that would be ideal for a gene transfer vector targeting the nervous system, an understanding of HSVE is of experimental, as well as clinical, .importance to neuroscientists. Herpesviruses have a characteristic architecture of the virion. The molecular aspects of HSVE include the consequences of latency and neurovirulence. Studies on neurovirulence have focused on peripheral multiplication of HSV, the invasion of the CNS, and growth in the CNS. The virus appears to gain access to the CNS via the olfactory and trigeminal nerves and, transneuronally, the limbic system. The definition of latency has still to be clarified; in general, latency includes three separable phases: establishment, maintenance, and reactivation. In humans, there exists a large overlap of clinical presentations of patients with HSVE and those of patients with encephalitis of other origin. However, the presence of memory loss, personality changes, and olfactory hallucinations correlate with the limbic and temporal lobe pathology in HSVE and are characteristic. Several factors correlate with poor outcome in patients: age, time of establishment of therapy, and level of consciousness on admission of patients. The Neuroscientist 2:44-54, 1996 KC/ WORDS Herpes simplex virus infections, CNS, Clinical, Evperimenta!Epidemiology of HSVE HSVE is a unique focal encephalitis, with a predilection for olfactory and limbic parts of the brain, that has an incidence of 1/250,000 to 1/300,000. This review concentrates on various aspects of HSV and HSVE, because this disorder is of interest both to clinical and basic neuroscientists and also because HSV's unique properties make it an excellent candidate as a gene transfer vector that targets particular parts of the brain. HSVE occurs throughout the year, one-third occurring in patients less than 20 years of age; one-half of the patients are more than 50 years of age. Mortality without treatment is 70%. Medical costs for hospitalization of HSVE patients alone are considerable, being over $25 million in the United States in 1983 (1). In adults and older children, HSVE is usually caused by HSV-1, whereas HSV-2 causes a benign lymphocytic meningitis. However, 6 of 93 consecutive Swedish cases of HSVE have been found to be caused by HSV-2 (2, 3). In newborns, HSV-2 causes ; I diffuse encephalitis, with or without systemic infection by HSV-2. Onethird of all cases of HSVE occur as primary infections in patients without a prior exposure to HSV. The majority of HSVE occurs in patients with preexisting antibodies, although only 10% of these have clinically Address reprint requests to: Ufa Meyding-Lamade. M.D.. Department of Neurology, University of Heidelberg. INF 400, 69120 Heidelberg, Germany.evident recurrent HSV infections, such as herpes labialis. Patients with primary infections are usually less than 18 years of age. HSVE does ...

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Pathogenicity of glycoprotein C negative mutants of herpes simplex virus type 1 for the mouse central nervous system

Cited by 23 publications

References 49 publications

Analysis of Herpes Simplex Virus ICP0 Promoter Function in Sensory Neurons during Acute Infection, Establishment of Latency, and Reactivation In Vivo

Analysis of Herpes Simplex Virus ICP0 Promoter Function in Sensory Neurons during Acute Infection, Establishment of Latency, and Reactivation In Vivo

A herpes simplex virus 1 recombinant lacking the glycoprotein G coding sequences is defective in entry through apical surfaces of polarized epithelial cells in culture and in vivo

HSV and the CNS

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