(57/226) Ocular herpes simplex virus infections: reduced sensitivity to acyclovir in primary disease.
Forty isolates of herpes simplex virus (HSV) obtained from ocular herpetic infections were assayed for their sensitivity to five antiviral agents. There were wide ranges of sensitivity to foscarnet, idoxuridine, and vidarabine, but the majority were sensitive to acyclovir and ganciclovir. Reduced sensitivity to acyclovir was seen in four isolates, all of which were from primary infections acquired in the community and without a previous history of treatment with antiviral drugs. (+info)
(58/226) HSV-2 alters retinal physiology and morphology bilaterally in mice.
Anterior chamber inoculation of 10(4) PFU of the MS strain of HSV-2 resulted in physiologic and morphologic changes in the retina of the inoculated and the uninoculated eyes. In the inoculated eyes, electroretinogram (ERG) depression was first detected on day 3 and abolished ERGs on day 8 postinoculation (PI). The decrease in the ERGs was rapid and the time course was similar for all of the eyes. In spite of a 90% decrease in the amplitude of the b-wave, the retinal sensitivity did not change. Of 23 eyes tested on or after day 10 PI, none had normal, 4.3% had reduced, and 95.6% had abolished ERGs. In the uninoculated eyes, ERG depression was first detected on day 8 and abolished ERGs on day 12 PI. The course of the ERG depression was more variable, and some of the eyes showed a decrease in retinal sensitivity. Of the 22 eyes tested on or after day 17 PI, 18% had normal, 32% had reduced, and 50% had abolished ERGs. The majority (17/33) of the retinas of the inoculated eyes showed panretinal necrosis, although 7 of 33 retinas had pathology confined to the outer layers of the retina. In the uninoculated eyes, only 5 of 30 retinas were necrotic and 14 of 30 retinas had pathology limited to the outer layers of the retina. These observations suggested that the physiologic and morphologic changes progress through two stages: an early stage with reduced ERGs and pathology limited to the outer retinal layers, and a second stage in which the ERG is abolished and the pathologic changes extend into the inner retina. Not all retinas progress to the second stage. (+info)
(59/226) Ocular safety and efficacy of an HSV-1 gD vaccine during primary and latent infection.
One potential complication of systemic herpes simplex virus (HSV) vaccination is that subsequent ocular infection may lead to increased immunogenic corneal scarring. Therefore, V52, a genetically engineered vaccinia virus that expresses the HSV-1 glycoprotein gD, was tested for ocular safety and for protection against ocular challenge with a stromal-disease-producing strain (McKrae) of HSV-1. To maximize immune response, rabbits were vaccinated by a series of inoculations. V52-vaccinated rabbits developed significant HSV-1 neutralizing antibody titers; however, they were not as high as those induced by vaccination with live HSV-1 McKrae. One month after the final vaccination, all rabbits were challenged ocularly. Eyes were monitored for 35 days for epithelial keratitis, stromal keratitis, and iritis. In no case was epithelial keratitis, stromal keratitis, or iritis significantly exacerbated by vaccination. The gD V52 recombinant vaccine provided protection against HSV-1 induced epithelial keratitis (P = 0.02) and long-term stromal scarring (P = 0.04). There was no significant reduction in the incidence of trigeminal ganglionic latency in the vaccinated rabbits (P greater than 0.05). Thus, our results indicate that V52, a gD recombinant vaccine probably is safe with regard to corneal scarring, and may provide a small amount of protection against ocular HSV-1 infection. The amount of protection provided was less than that reported in mice and guinea pigs. This suggests that to provide high levels of ocular protection in rabbits (and probably in humans), HSV-1 vaccines may have to elicit a more vigorous immune response than that produced by normal HSV-1 infection. (+info)
(60/226) The effect of flurbiprofen on herpes simplex virus type 1 stromal keratitis in mice.
The use of steroidal compounds to reduce the inflammation and scarring associated with herpes simplex virus type 1 (HSV-1) stromal keratitis can result in severe exacerbation of the corneal disease. We compared the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen sodium with dexamethasone for the treatment of HSV-1 induced corneal stromal disease in an inbred mouse model. Stromal disease was induced by the direct intrastromal injection of HSV-1. A stromal opacity and corneal neovascularization (CNV) developed in 100% of the injected eyes, with no epithelial involvement until late in the course, when the stromal disease was quite severe, such that it was possible to test the effectiveness of drugs in animals with an intact epithelium. Dexamethasone treatment had a variable effect on the severity of disease, ranging from a significant reduction in severity to significant exacerbation of disease, compared with placebo-treated controls. The most frequent effect of dexamethasone treatment was a worsening of corneal stromal opacities and CNV. In contrast, treatment with the NSAID did not exacerbate HSV-1 stromal disease. Flurbiprofen treatment resulted in a significant reduction of the maximum intensity of stromal opacity in some experiments, whereas in other experiments the effect was not statistically significant. In vitro studies of the effect of the anti-inflammatory drugs on HSV-1 replication in Vero cells revealed that both dexamethasone and flurbiprofen inhibited HSV-1 replication in a dose-dependent manner. Flurbiprofen had a greater inhibitory effect, which appears to be due, at least in part, to a direct virucidal effect. Dexamethasone did not exhibit virucidal activity.(ABSTRACT TRUNCATED AT 250 WORDS) (+info)
(61/226) Antiviral drug sensitivity in ocular herpes simplex virus infection.
Thirty-nine herpes simplex virus (HSV) isolates were assayed for their sensitivity to 10 different antiviral agents. Of these 39 HSV isolates 10 were cultured from recipient buttons obtained at penetrating keratoplasty in patients with inactive stromal scarring due to recurrent herpetic keratitis, 25 were cultured from patients with conjunctival and ulcerative ocular infections, and the remaining four were laboratory strains with known drug sensitivity patterns, thus providing controls for the experiment. All but one of the 35 clinical isolates of HSV were type 1 and all were sensitive to the 10 antiviral agents. A single type 2 isolate from a young man with recurrent conjunctivitis proved to be resistant to a number of the antiviral agents. Since many of the clinical isolates had been exposed to multiple and protracted antiviral drug treatment, it is suggested that antiviral drug resistance in type 1 HSV ocular infection is not a significant problem. (+info)
(62/226) Contribution of virus and immune factors to herpes simplex virus type I-induced corneal pathology.
In vivo T-lymphocyte subpopulation depletion techniques were used to identify the roles of L3T4+ (CD4) and Lyt-2+ (CD8) T-lymphocytes in the pathogenesis of corneal stromal disease induced by two different strains of Herpes simplex virus type 1 (HSV-1). Histologic examination of infected corneas revealed significant differences in the composition of the inflammatory corneal infiltrates induced by the RE and KOS strains of HSV-1. The RE strain induced a predominantly polymorphonuclear leukocyte (PMN) infiltrate, which began approximately 1 week after infection and progressed through day 21. Depletion of CD4 cells before corneal infection with RE HSV-1 greatly reduced the incidence and severity of corneal disease; depletion of CD8 cells had no effect. The strain KOS HSV-1 induced an early PMN infiltrate that became predominantly mononuclear by day 21. Depletion of CD4 cells did not change the incidence or severity of KOS HSV-1-induced corneal stromal disease. The corneal lesions of these mice contained numerous CD8 cells. Depletion of CD8 cells before KOS HSV-1 infection of the cornea moderately reduced the incidence of stromal disease. However, in CD8-depleted mice with the disease, PMNs were the most prevalent infiltrating cells, and the disease appeared identical to that seen in RE HSV-1 infected corneas. Simultaneous depletion of CD4 and CD8 cells before KOS HSV-1 infection eliminated stromal disease. However, when T-cell depletion was discontinued in these mice, stromal disease developed in concert with the appearance of T-cells in the lymphoid organs and corneas. Thus, T-lymphocytes are a necessary component of HSV-1 corneal stromal disease. These results further suggest that RE HSV-1 preferentially activates CD4 cells in the cornea, and KOS HSV-1 preferentially activates CD8 cells in the cornea. (+info)
(63/226) Mixed infection with herpes simplex virus type 1 generates recombinants with increased ocular and neurovirulence.
The authors used the method of mixed ocular infection and subsequent in vivo selection to isolate Herpes simplex virus type 1 intratypic recombinants with increased ocular virulence and neurovirulence. Four recombinants were studied in some detail (DRG1A3, DRG2A2, DRG3A3, and DRG4A1). The recombinants had lethal doses in 50% of animals tested (LD50) at least 2-3 log units lower than either parent virus (OD4 and CJ394) and caused significantly more severe stromal keratitis, vascularization of the cornea, and blepharitis than either parent. Studies on the ability of DRG1A3 and DRG4A1 to replicate in the eye, trigeminal ganglia, and brain showed that these recombinants replicated to higher titers (1-3.5 log units) than the parents in all three tissues. One of the parents, OD4, spread to the central nervous system with the same kinetics as CJ394, DRG1A3, and DRG4A1 but had a restricted ability to replicate in all tissues, which may account for its lack of virulence. The other parent, CJ394, was nonneurovirulent but replicated to titers which were only 1-1.5 log units lower than the neurovirulent recombinants. These recombinants should be useful in studying virulence determinants in herpetic ocular infections. (+info)
(64/226) Pathogenesis of corneal oedema associated with herpetic eye disease.
Corneal oedema and stromal disease, induced in rabbits by intrastromal injection of herpes simplex virus, type 1, strain RE (HSV-1, RE), reached a peak of 12-15 days after infection. Corneal oedema as measured by ultrasonic pachymetry, and stromal disease as measured by a subjective scoring system, were closely related for 30 days after infection. Morphometric analysis of wide field specular micrographs showed that no immediate endothelial cell damage occurred in either control or HSV-1 infected corneas. Alizarin red S staining of corneas taken during the period of most severe oedema indicated no significant endothelial cell loss; however, visual inspection indicated numerous staining abnormalities. Scanning and transmission electron microscopy provided evidence of an intact endothelial layer possessing integrated infiltrating cells. Virus antigen could not be detected on endothelial cells by immunoperoxidase staining at any time during development of corneal oedema. The results indicate that corneal oedema associated with HSV-1 induced disease can occur in the absence of detectable virus replication and cytolysis of corneal endothelial cells. (+info)