摘要:

The neurotropic herpes viruses, as typified by herpes simplex virus type 1, are noted for their ability to form latent infections. The latent infection differs from the acute infection both in gene expression and the physical state of the viral genome. Latency can be divided into several stages - establishment, maintenance of reactivation - each of which are active areas of research. This review describes the molecular biology of HSV-1 latency and presents the current level of understanding of the molecular mechanism of HSV-1 latency.

ISSN:0271-3683    

DOI:10.3109/02713689109020352

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Polymerase chain reaction (PCR) assays were used to amplify herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) sequences in DNA extracted from formalin-fixed, paraffin embedded corneas of patients undergoing corneal transplantation. PCR reamplification with an internal (nested) set of primers was required for detection in 10 of the 12 positive corneas indicating very low abundance of viral sequences. Three of the positive corneal samples were from failed corneal grafts. Overall, TK sequences were detected in 8 of 11 corneas from subjects with a past history of herpes keratitis and in 4 of 11 corneas from subjects with no past history of herpetic eye disease.

ISSN:0271-3683    

DOI:10.3109/02713689109020353

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Four days after corneal inoculation of mice with herpes simplex (type 1) virus (HSV), infected trigeminal ganglion cells with and without calcitonin gene-related peptide (CGRP) antigenicity were examined by electron microscopy in sections treated with colloidal gold labeled antibodies. Cells that contain CGRP were identified by the dense gold labeling of small vesicles about 100 nm in diameter. Adjacent thin sections were stained using an indirect colloidal gold immunocytochemical technique to reveal HSV-1 antigens. In CGRP-positive neurons, HSV antigens were located over both nuclear and cytoplasmic compartments. HSV label was found over cytoplasmic vesicles that were significantly larger than those labeled with anti-CGRP antisera; the HSV-containing vesicles ranged in profile diameter from less than 170 to greater than 400 nm. There was no overlap in the distribution of the two labels. Thus, for this time period, the organelles involved in transport of the endogenous neuropeptide and HSV appear to remain discrete. Furthermore, there was no significant difference in the distribution of HSV in CGRP-reactive and CGRP-negative trigeminal ganglion cells. Thus, there is no indication of a preferential distribution or limited replication of HSV in CGRP-positive neurons.

ISSN:0271-3683    

DOI:10.3109/02713689109020354

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

A intertypic recombinant, designated HSV-R(D1), had previously been generated from non-neuroinvasive HSV-2(186) and neuroinvasive HSV-1(17). Although the recombinant contained<2% of the HSV-1 genome, it retained the neuroinvasive phenotype. The nucleotide sequences responsible for the neuroinvasiveness of HSV-R(D1) were previously mapped to a 3.0 kb segment of DNA located within the DNA polymerase gene (mu 0.414 to 0.430) via marker rescue experiments. We have now sequenced this region and compared our results to the published nucleotide sequence of the HSV-1 (17) and HSV-2(186) DNA polymerase genes. It was found that the 3.0 kb HSV-R(D1) DNA fragment consisted entirely of HSV-2(186) nucleotide sequences except for the presence of 1610 bp of HSV-1 (17) DNA. The 1610 bp of HSV-1 DNA coded for a 536 amino acid (AA) region which were located between AA 254 and 790 of the DNA polymerase enzyme. Comparison of the 536 AA sequence of neuroinvasive HSV-1 (17) with the homologous area of the non-neuroinvasive HSV-2(186) DNA polymerase indicated that the two polymerases differed at 56 AA positions. In addition, this area of the HSV-1 (17) DNA polymerase was 5 AA acids shorter than the HSV-2(186) DNA polymerase. Specific amino acid changes that might account for the neuroinvasive phenotype of HSV-R(D1) are discussed.

ISSN:0271-3683    

DOI:10.3109/02713689109020355

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

An intertypic recombinant isolated from rabbit kidney cells following co-transfection of HSV-1(17) and HSV-2(186) DNA failed to induce overt ocular pathology when inoculated onto the murine scarified cornea at concentrations as high as 107PFU per eye. In contrast, both parents induced corneal disease at a 1000-fold lower dose. The reason (s) for the failure of the intertypic recombinant, designated R025X, to induce corneal pathology was investigated. It was found that the recombinant was 100-fold more sensitive to the inhibitory effects of interferon (FN)α/βthan the parent strains in corneal button growth studiesin vitro.R025X readily grew in cultured mouse corneal fibroblasts at a low multiplicity of infection. However, the peak titer was approximately 8-fold lower than that of strain 17. Addition of rabbit anti-IFNα/βto the culture medium resulted in a 4 to 5-fold increase in infectious titer compared to its growth in the absence of antiserum. Most significantly, when mice were pre-treatedin vivowith anti-IFNα/β24 hours prior to virus corneal infection, 67% of the recipients developed moderate to severe stromal keratitis, whereas none of the controls developed corneal pathology. Blepharitis was also significantly increased in incidence and severity in the antiserum treated hosts. We conclude that the inability of R025X to induce ocular disease was due, at least in part, to the inhibitory effects of interferon produced in response to infection.

ISSN:0271-3683    

DOI:10.3109/02713689109020356

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

In these studies, mice were simultaneously depleted of CD4 and CD8 T lymphocytes (T cell-depleted) by weekly intraperitoneal injections of rat monoclonal antibodies specific for L3T4 and Lyt-2 respectively, beginning 1 day before topical corneal infection with KOS herpes simplex virus type 1 (HSV-1). Control mice were mock-depleted by weekly injections of saline. All mice developed dendritic epithelial lesions 2-3 days after infection, which healed within 2 days. Fifty percent of the mock-depleted mice developed severe HSV-1 stromal disease, which began 9-14 days after infection. No skin lesions were observed in mock-depleted mice. In contrast, none of the T cell-depleted mice developed HSV-1 corneal stromal disease through an initial 30 day observation period. These mice did develop severe periocular skin lesions. After 30 days, the T cell-depleted mice were subdivided into two groups. In one group, T cell depletion was continued and the mice remained largely free of stromal disease for an additional 30 days (one of 30 mice developed a mild stromal haze). T cell depletion was discontinued in the second group. During the subsequent 30 days the CD4 and CD8 T cells in their lymph nodes and spleens recovered to approximately 50% of normal, and 43% (13 of 30) of the mice developed severe HSV-1 stromal disease. The skin lesions healed in all T cell-depleted mice between days 30 and 60, even when T cell depletion was maintained. Our findings demonstrate that T cells are both protective (preventing the spread of HSV-1 in the skin) and detrimental (inducing the destruction of the corneal stroma). Viral antigens seem to persist for at least 30 days in an apparently normal cornea but induce disease only when the cornea is infiltrated by HSV-1 reactive T lymphocytes.

ISSN:0271-3683    

DOI:10.3109/02713689109020357

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

The protective role of T cell subsets in corneal herpes simplex virus type 1 (HSV-1) infection has been studied. However, the relative contribution of, and the role played by, each particular T cell subset still remain a controversial issue.We studied sequentially the appearance of major histocompatibility (MHC) and viral antigens in HSV-1 infected corneas of Balb/C mice and related them to induction of T cell subsets in local lymph nodes and corneal lesions. Immunohistochemical study has revealed a marked increase of expression of class II MHC antigen in the corneal stromal cells, while class I MHC antigen gradually increased in the corneal epithelium and stroma. Further immunohistochemical survey has revealed that L3T4, antigen bearing and Lyt 2 antigen bearing cells were induced to a similar extent with an equal rapidity in the local lymph nodes as well as in the corneal stroma. Transfer of these subpopulations to syngeneic nude mice showed that they played a role to prevent severe outcome of corneal herpetic infection.These results indicate that the corneal stroma is a major site of the host's immunological activities and both L3T4, and Lyt 2 bearing cells are equally important for the prevention of corneal herpetic infection.

ISSN:0271-3683    

DOI:10.3109/02713689109020358

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Fifty-one corneal buttons obtained by penetrating keratoplasty from patients with a preoperative clinical diagnosis of nonulcerative herpetic keratitis and/or disciform stromal scarring (44) as well as ulcerative necrotizing stromal keratitis (7) were processed for herpes simplex virus (HSV) antigens using an immunoperoxidase technique and for HSV DNA by the polymerase chain reaction (PCR). HSV antigens were detected significantly more often (p<0.025) in specimens with avascular nonulcerative keratitis than in those with vascularization. In contrast to HSV antigens, HSV DNA was identified at equal proportions in avascular and vascularized lesions. Both HSV antigens and HSV DNA were detected in all specimens from patients with ulcerative necrotizing stromal keratitis. The implications of these findings with regard to possible mechanisms underlying herpetic keratitis in man are discussed.

ISSN:0271-3683    

DOI:10.3109/02713689109020359

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Infection on the snout with HSV-1 in mice with normal corneas produced a mild ocular disease, characterized by a zosteriform skin lesion around the eye, enlargement of the pupil, hyperemia of the iris and, sporadically, transient keratitis. By contrast, snout infection after prior cauterization of the cornea induced significantly more frequent and more severe corneal disease, in which keratitis was usually permanent. Corneal cauterization also produced increased numbers of Langerhans cells in the central cornea. We speculate that the combination of virus and increased numbers of Langerhans cells within the cornea may lead to an exaggerated ocular immune response that is destructive to the cornea.

ISSN:0271-3683    

DOI:10.3109/02713689109020360

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

After uniocular anterior chamber inoculation of the KOS strain of HSV-1 in BALB/c mice, acute retinal necrosis develops in the uninoculated eye. These mice exhibit suppression of virus-specific delayed hypersensitivity which is the hallmark of anterior chamber associated immune deviation (ACAID). In contrast, inoculation of C57BL/6 mice with KOS induces vigorous virus-specific DTH, and there is no retinal necrosis in the uninoculated eye. We performed experiments using RH116, a mutant of KOS and SC16, a neurovirulent strain of HSV-1, in BALB/c and C57BL/6 mice to examine whether virus or host factors determine the outcome of anterior chamber inoculation of HSV-1 (ACAID or DTH, retinal necrosis or retinal preservation). We found that high titers of virus ($105) within the first 24 hours in the inoculated eye were linked to the induction of ACAID and that the induction of ACAID following anterior chamber inoculation of HSV-1 is neither an exclusive feature of a strain of virus nor is the ability to develop ACAID a distinguishing characteristic of an individual strain of mice. Taken together, our findings suggest that the interplay of both virus and host factors results ultimately in acute retinal necrosis following anterior chamber inoculation of HSV-1 in the mouse.

ISSN:0271-3683    

DOI:10.3109/02713689109020361

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor