摘要:

In this discussion, strategies for physically mapping HSV gene functions associated with significant biologic effects are presented and discussed. They represent an application of molecular biological technologies to complex biologic systems, and are a beginning step in understanding the fundamental basis of herpetic disease. Future studies will involve precise identification of relevant genes, and studies of the important properties of products encoded by these genes.

ISSN:0271-3683    

DOI:10.3109/02713688709020070

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

The corneal discs of 41 patients with scarring reminiscent of herpetic infection were organ cultured for HSV isolation. Of the 41 patients, 34 had a definite history of herpetic keratitis, from 10 of whom (29.4%) HSV was isolated. There were no clinical features which distinguished between these groups; there was however an indication that those from whom HSV was not isolated had been previously treated with substantial amounts of topical acycloguanosine. In three patients of 12 patients when the disc was separated into 7 parts using a punch technique, virus was isolated exclusively from those portions demonstrating clinical scarring. Electron microscopy (EM) demonstrated HSV particles in stromal cells in the cultured corneas of seven patients. In two of the patients no virus was detected prior to culture with EM. In one patient HSV antigen was not found using peroxidase-antiperoxidase (PAP) staining prior to subsequently positive organ culture.Studies were made to determine how HSV accedes to the corneal stroma using a murine model in which keratitis occurs by zosteriform spread of HSV following inoculation of the snout. Preliminary evidence using PAP staining indicates that the virus reaches the stroma at the same time as the epithelium, via the sensory nerves. Evidence of HSV persistence in anterior segments was obtained in the same model, in contrast to which no virus could be isolated following direct inoculation into the cornea. It is speculated that for virus to set up a longterm association with the stromal keratocyte, it must be introduced via the sensory nerve. It is proposed that the original source of stromal virus lies in the stroma beneath the dendrite, and that spread of virus from this site occurs by intercellular spread, rather than by extracellular spread from the ulcerated epithelium.

ISSN:0271-3683    

DOI:10.3109/02713688709020071

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

A modified, bilateral iontophoresis technique was used to evaluate herpes simplex virus (HSV) reactivation and epinephrine distribution and concentration in full-thickness corneas and in trigeminal ganglia of rabbits. Infectious virus was recovered from 58% of epinephrine-induced eyes 24-96 hours after iontophoresis. A histochemical adrenochrome oxidation method localized epinephrine exclusively in the corneal epithelium and anterior stromal lamellae after iontophoresis. Epinephrine introduced iontophoretically into the corneal epithelium and stroma did not reach the ganglion level as detected by the assay. Radiometric-enzymatic assay of corneal and ganglionic tissues demonstrated a transient increase in total corneal catecholamine levels from an average of 417 ug to an average of 778 ug; concentrations returned to approximate control values 24 hours after iontophoresis. Ganglion total catecholamine levels increased from an average of 606 ug to an average of 1211 ug for a 12-hour period and remained elevated at 24 hours after iontophoresis. Epinephrine acting directly on the corneal epithelium and epinephrine metabolites at the ganglion level could act synergistically to induce ocular and ganglionic HSV reactivation.

ISSN:0271-3683    

DOI:10.3109/02713688709020072

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Recurrent herpetic keratitis remains a major cause of corneal blindness in developed countries. A fundamental unanwered question regarding herpes simplex virus infection concerns the relationship between the virus and host cell DNA during latency. In the present study DNA was extracted from trigeminal ganglia during both acute and latent infection following ocular inoculation. Extracted, purified DNA was utilized for transfection and for hybridization studies using a32P-labeled HSV-1 DNA probe. DNA extracted during acute infection was complete, linear and non-integrated. Autoradiographic patterns of DNA isolated during latent infection were suggestive of two separate DNA species.

ISSN:0271-3683    

DOI:10.3109/02713688709020073

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Spontaneous ocular shedding and adrenergic induction of ocular shedding were examined in rabbits infected with ten strains of herpes simplex virus type 1 (HSV-1): McKrae, KOS, F, Rodanus, 17 Syn+, RE, E-43, SC-16, MacIntyre, and CGA-3. All ocular inoculations were with 50μ1 of HSV-1 with titers between 1-10×106PFU/ml. All corneas, except those that received the McKrae strain, were scarified. Acute ocular infection was determined by slit-lamp biomicroscopy. Dendritic keratitis or geographic ulcers developed in all eyes of all rabbits within 10 days after ocular inoculation. All eyes of all surviving rabbits were swabbed for 20 consecutive days during days 20-39 postinoculation (PI). On PI day 19, no active lesions were present as judged by slit-lamp biomicroscopy. Ocular tear film was collected on a Dacron-tipped swab and placed on primary rabbit kidney cell monolayers. The cell monolayers were monitored for cytopathic effects consistent with HSV-1 infection. Spontaneous HSV-1 shedding was detected in some eyes from all groups of latently infected rabbits, except those infected with CGA-3. Spontaneous shedding (positive swabs/total swabs) of the other nine strains ranged from 0.7% to 15.7%.After PI day 42, the rabbit eyes received 6-hydroxydopamine by iontophoresis, followed for 5 days by topical application of 2% epinephrine. This procedure results in induced HSV-1 ocular shedding for a duration of 3-5 days in rabbits infected with the McKrae strain. In rabbits latently infected with KOS, F, RE, MacIntyre, and CGA-3, no induced HSV-1 shedding was detected. In addition to the McKrae strain, 17 Syn+, E-43, and SC-16 strains could be adrenergically induced to shed virus. All eyes of rabbits latently infected with Rodanus shed virus spontaneously, however, no induction occurred. Co-cultivation of the trigeminal and superior cervical ganglia revealed that all ten strains were present in the latent phase in these neural tissues.For all strains, the frequencies of recovery of latent HSV-1 from the trigeminal and superior cervical ganglia were the same regardless of whether the corresponding eye shed virus or did not shed virus.We conclude that all these strains of HSV-1 develop neural latency at about the same frequency. Furthermore, ocular reactivation is strain-specific and can be separated into an endogenous (spontaneous) and exogenous (induced) event.

ISSN:0271-3683    

DOI:10.3109/02713688709020074

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Induction of HSV lesion recurrence may be achieved by a variety of stimuli. Trauma of almost any kind (physical, chemical, electromagnetic and thermal) to the healed primary lesion site has been successful for induction of recurrence (1). In common with each of these mechanisms is the release of inflammatory mediators (arachidonic acid (AA), complement, kinins, etc.) following trauma. Because blockade of the AA cascade with steroids has been noted to abort HSV skin lesions (2), and because steroids have numerous side effects making them a poor therapeutic choice in ocular lesions, we decided to test several relatively different types of AA cascade inhibitory drugs in mouse ear HSV recurrence models (3). In this series of experiments, it was found that topical steroids gave the greatest initial decrease in lesion number (80% fewer than control on day 3 post recurrence induction (PRI), while meclofenamate resulted in the greatest reduction of lesions by day 5 PRI (85% fewer lesions than control and 60% fewer than the steroid treated group). The NDGA treated group exhibited the least reduction in recurrence severity (27% fewer lesions than control on day 5 PRI and 200% more lesions than the steroid group. Chlorpromazine (thorazine) acted roughly equivalent to the steroid treated group by day 5 PRI (70% fewer lesions than the untreated control group). Relative efficacy in lesion reduction between grops by day 5 PRI is: meclofenamate>steroid = chlorpromazine>NDGA>control. Meclofenamate, steroid and chlorpromazine significantly reduced lesions (p<. 05) when compared with the saline treated control mice. NDGA did not significantly reduce lesions by day 5 PRI.

ISSN:0271-3683    

DOI:10.3109/02713688709020075

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

Since the herpes simplex virus locates latently in the ganglia and is reactivated by certain triggers, the important problem in treatment is to prevent or reduce recurrence.The present study investigates the role of mechanical debridement in lessening the recurrence of dendritic keratitis in patients with herpetic epithelial keratitis. Group A was treated with mechanical debridement plus IDU, Group B with IDU alone.Also studied was the effect of steroid subconjunctival injection on herpetic recurrence in patients with herpetic stromal keratitis: Group C was treated with intravenous infusion of pepsin-treated gamma-globulin (PTGG) and steroid subconjunctival injection, Group D with steroid subconjunctival injection alone and Group E with intravenous infusion of PTGG alone.The recurrence rates of dendritic keratitis were 19% in Group A and 40% in Group B (average follow-up periods: 24 and 25 months).The recurrence rates of stromal keratitis were 61% in Group C, 64% in Group D, and 36% in Group E (average follow-up periods: 20, 19 and 15 months). The difference between Groups D and E was statistically significant (x2test, P<0. 05). The recurrence rates of dendritic keratitis were 18% in Group C, 21% in Group D and 7% in Group E.In conclusion, mechanical debridement tended to reduce the recurrence of herpetic epithelial keratitis and steroid subconjunctival injection to increase the recurrence of epithelial or stromal keratitis.

ISSN:0271-3683    

DOI:10.3109/02713688709020076

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

The application of 6-hydroxydopamine to the cornea by iontophoresis, followed by topical epinephrine, effectively induces herpes simplex virus (HSV) shedding from the external eye of latently infected rabbits. In this study the beta adrenergic blocker, Timolol, reduced virus shedding when applied immediately before the epinephrine, but continued administration resulted in increased viral shedding. While indomethacin, a prostaglandin synthesis inhibitor decreased HSV replication in cell culture, it failed to decrease virus shedding when applied topically to the eye in adrenergically stimulated animals. Timolol may act then by its effect on the peripheral cells of the eye rather than by stimulation of virus production in ganglionic neurons. These same animals were subsequently tested for latent infection of the trigeminal and superior cervical ganglia and corneas 14 months after primary infection. Only 2 of 14 animals had virus in the trigeminal ganglia, a finding which suggests that latent virus may be depleted by repeated reactivations. Virus was recovered from corneas of five rabbits by co-cultivation so it is possible that corneal latency occurs in this rabbit model as it does in humans.

ISSN:0271-3683    

DOI:10.3109/02713688709020077

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

ICR mice were inoculated intracamerally with McKrae strain herpes simplex virus (HSV) followed by intraperitoneal injection with 3H-thymidine. Infected mice were sacrificed after 3 or 4 days and the eyes, trigeminal ganglia (TG) and superior cervical ganglia (SCG) were embedded in glycol methacrylate, sectioned, and dipped for autoradiography. Light microscopy revealed silver grain labeling over neurons in the ipsilateral retina, TG and SCG of infected animals. No label ing of neurons was noted in the contralateral TG or SCG. Since the DNA of mature neurons does not replicate, we interpret these labeled neurons to represent cells with active replication of HSV. This technique allows the study of HSV infection of the nervous system with excellent tissue preservation. Furthermore, it may be used to distinguish those neurons with intrinsic viral synthesis from those harboring virus synthesized at a distant site with subsequent intracellular spread.

ISSN:0271-3683    

DOI:10.3109/02713688709020078

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor

摘要:

To test the hypothesis that ACAID induction is instrumental in producing the distinctive pattern of retinal pathology that follows anterior chamber inoculation of HSV-1 in BALB/c mice, panels of mice received uniocular anterior chamber, uniocular intravitreal, and bilateral anterior chamber inoculations of HSV-1. It was found that contralateral retinitis developed after the first two routes, and ACAID was induced by all three. Enucleation of eyes inoculated with HSV-1 before 3 days post-inoculation(but not thereafter) prevented both ACAID and contralateral retinitis. Intracameral inoculations of HSV-2 induced vigorous delayed hypersensitivity and failed to incite contralateral retinitis. It is concluded that ACAID induction plays a crucial role in the pathogenesis of contralateral retinitis following anterior chamber inoculation of HSV-1.

ISSN:0271-3683    

DOI:10.3109/02713688709020079

出版商:Taylor&Francis    

年代:1987

数据来源: Taylor