Control of Stromal Keratitis by Inhibition of Neovascularization

Stromal keratitis resulting from ocular infection with herpes simplex virus is a common cause of blindness. This report investigates the role of neovascularization in the pathogenesis of stromal keratitis by measuring the outcome of treatment with the potent anti-angiogenesis cytokine endothelial monocyte-activating polypeptide II (EMAP II). We show that systemic and topical administration of EMAP II from the outset of infection resulted in markedly diminished levels of herpes simplex virus-induced angiogenesis and significantly reduced the severity of stromal keratitis lesions. EMAP II treatment had no demonstrable pro-inflammatory or toxic effects and failed to express antiviral activity. The mechanism of action of EMAP II was shown to proceed by causing apoptosis in vascular endothelial cells. Our data document for the first time the essential role of angiogenesis in the pathogenesis of stromal keratitis and also indicate that the therapy of herpetic stromal keratitis could benefit by procedures that diminish angiogenesis.     

New antiviral drugs that target herpesvirus helicase primase enzymes

Herpesviruses have infected the majority of the world's population and the associated diseases have plagued humanity since ancient times. Nine causative human herpesviruses have been identified so far. The first antiviral drug was launched in 1962, and since then several drugs for treating herpesvirus infections, which work via different mechanisms, have been developed. Current treatments abrogate or suppress disease symptoms but are not curative. A vaccine based on the OKA strain of varicella zoster virus is being marketed, but to date no therapeutic or prophylactic herpes vaccinations that can treat or stop spread of other herpes diseases are available. Herpes simplex virus causes mucocutaneous infections such as herpes genitalis (genital herpes) and herpes labialis (cold sores), the potentially sight-impairing herpetic eye disease, and life-threatening herpes encephalitis or disseminated disease. Recently, reports of helicase primase inhibitors, the first non-nucleosidic antiviral compounds, which are superior in pre-clinical profile to current herpes simplex virus medication, have been published. This review summarizes the data on helicase primase inhibitors and compares their pre-clinical profile with the established medical standard.     

Herpes and retinal lesions: what's new?

The viral retinitis are linked to infection by herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV). When the diagnosis is clinically suspected the antiviral treatment has to be introduced immediately after performing the ocular sampling to try to identify the infectious agent. Despite the various antiherpetic drugs available by intravenous routes and intravitreal injection, the prognostic of the herpetic retinitis remained severe because of the occurrence of retinal detachment, optic neuritis, macular necrosis. Various clinical forms are described: (1) the classical "acute necrotizing retinitis" (2) a form with a slow progression of the necrotizing retinitis (3) occlusive retinal arteritis (4) the highly severe "progressive retinal necrosis". The incidence of the CMV retinitis diminished with the highly antiretroviral therapy; however uveitis may occur with no active CMV retinitis. The various antiherpetic drugs are described with special indications.     

Levels of T lymphocytes, but not specific antibodies, reflect clinical presentation in human herpes simplex keratitis

Total erythrocyte Rosette-forming cells (ERFC) have been found to be decreased in 44 patients with recurrent ocular herpes but normal in 26 patients with the primary form of the disease. Active ERFC have been found to be decreased in 27 patients with herpetic keratouveitis and normal in 43 patients with superficial herpetic keratitis. Antibodies to herpes simplex virus could not be used to distinguish the various clinical presentations of the disease.     

Isolation of herpes simplex virus in chronic meningoencephalitis

Virological examination of a patient suffering from chronic meningoencephalitis was carried out using serological and morphological methods. Strains of herpes simplex virus were isolated from the saliva, cerebrospinal fluid, and blood of the patient simultaneously in white mice and tissue culture. A rise in antibody titers to the isolate, its high neuropathogenicity in animal inoculation experiments, and the results of pathomorphological studies confirm the herpetic nature of the neuroinfection in this patient. Serological identification and investigation of biological properties of the virus showed it to belong to the 2nd antigenic type of herpes simplex virus.     

重组人干扰素α2b喷雾剂的抗病毒药效评价及临床观察

目的研究重组人干扰素α2b喷雾剂抑制单纯疱疹病毒、流感病毒、SARS冠状病毒有效浓度范围,为临床研究提供依据并进行治疗病毒性皮肤疾病临床验证。方法采用细胞病变抑制法研究重组人干扰素a2b喷雾剂抑制单纯疱疹病毒HSV-1及HSV-2攻击Vero细胞,抑制流感甲型及乙型病毒攻击人胚肾细胞,抑制SARS冠状病毒攻击Vero细胞的体外抗病毒作用。采用多中心、随机双盲临床试验评价重组人干扰素α2b喷雾剂对流感甲型及乙型病毒、尖锐湿疣的治疗效果。结果重组人干扰素a2b喷雾剂抑制单纯疱疹病毒HSV-1及HSV-2对Vero细胞的攻击的半数有效浓度（IC50）分别为81．2IU／ml和390．0IU／ml;重组人干扰素α2b喷雾剂抑制流感甲型及乙型病毒对人胚肾细胞攻击的IC50分别为534．1IU／ml和3645．5IU／ml;抑制SARS冠状病毒对Vero细胞攻击的IC50为11．77IU／ml。多中心、随机、双盲的临床研究表明,重组人干扰素α2b喷雾剂治疗单纯疱疹的有效率为89．09％,治疗尖锐湿疣有效率为22．0％,治愈率为17．0％,患者均未见明显不良反应。结论体外实验表明重组人干扰素α2b喷雾剂对单纯疱疹病毒、流感病毒、SARS冠状病毒有显著抑制作用,临床研究表明重组人干扰素α2b喷雾剂作为蛋白经皮给药制剂可用于单纯疱疹和尖锐湿疣的临床治疗。     

The Potential Role of Polymerase Chain Reaction in Diagnosis of Neonatal Herpes Simplex Virus Infection: Is Viral Culture Outdated?

Even in the era of effective antiviral therapy, neonatal herpes simplex viral infection causes significant morbidity and mortality in newborns. Prompt diagnosis is the cornerstone of treatment of these infants. Outside and inside the neonatal clinical practice, polymerase chain reaction (PCR) is replacing culture as a method of facilitating a speedy diagnosis of herpes simplex virus infection. New pediatric guidelines call for testing of high-risk asymptomatic infants, and thus, many more surface cultures and PCRs are being performed. This review aims to comprehensively describe the perinatal transmission of herpes simplex virus infection and the clinical presentation of neonatal herpes simplex disease, as well as to discuss whether PCR remains superior to culture methods.     

Herpetic infection of the oral cavity in guinea pigs]

A convenient experimental model for serial studies of herpes simplex of the buccal mucosa has been developed in guinea pigs by application of fresh isolates of herpes simplex virus type 1 from a patient with primary herpetic gingivo-stomatitis on prescarified buccal mucosa. The herpetic nature of the eruptions in the oral cavity was confirmed by virus isolations and serologically. The possibility of exogenous reinfection of the buccal mucosa in convalescent animals against the background of humoral virus-neutralizing antibody has been demonstrated. No virus was isolated from the blood, brain, regional lymph nodes, oesophagus, trachea, lungs or liver of the animals with primary herpes simplex of the buccal mucosa. The model is recommended for experimental investigations of herpetic infections of the buccal mucosa.     

Pathogenetic aspects of severe course of herpetic infection

We studied the state of antiviral defense in patients with severe course of herpetic infection of anogenital and labial localization and the frequency of its combination with other herpes virus infections. It was found that severe course of herpetic infection caused by herpes simplex virus occurs against the background of combined secondary immunodeficiency and its complication. We first demonstrated that severe course of the disease is associated with mixed viral infection. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Supplement 2, pp. 76–81, April, 2007     

Therapeutic effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine, caffeic acid oxidation product, and trisodiumphosphonoformate on cutaneous herpes simplex virus type 1 infection in guinea pigs

The influence of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), caffeic acid oxidation product (KOP), and trisodiumphosphonoformate (TPF) on the course of the primary cutaneous herpes simplex virus infection was investigated by means of a guinea pig test model. The antiviral substances were applied in an ointment with 10% urea as a penetration mediator. When the treatment was initiated 15 minutes after virus inoculation, 3% BVDU effectively inhibited the development of herpetic vesicles and 0.1% BVDU prevented the appearance of herpetic satellites. Under the same conditions 1% and 3% KOP ointments inhibited the appearance of satellites; and 0.5% TPF ointment completely inhibited the development of cutaneous herpes lesions. Prophylactic drug administration given 24, 20, and 4 hours before virus inoculation was without any protective effect.     

Comparison of the sensitivity of a 24 h-shell vial assay, and conventional tube culture, in the isolation of Herpes simplex virus – 1 from corneal scrapings

Background  

Herpes simplex keratitis is a sight threatening ocular infection. A rapid and specific diagnosis is essential for the institution of specific antiviral therapy and to avoid complications that can arise from misdiagnosis and inappropriate treatment. Though a variety of techniques are available, isolation of Herpes simplex virus 1 (HSV-1) in culture provides the most reliable and specific method, and is considered as the gold standard in laboratory diagnosis of herpes simplex keratitis. We report a comparative study of the sensitivity of a 24 h-shell vial assay and conventional tube culture in the isolation of HSV-1 from corneal scrapings.     

The effect of trauma on production of herpes interferon in guinea pigs

Summary An appreciable amount of serum and skin interferon was produced in guinea pigs during herpes simplex virus infection. When such guinea pigs were subjected to various experimental trauma the production of interferon was generally decreased. Systemic and local injections of purified interferon confered definite protection against herpes simplex virus infection by the cutaneous, peritoneal and intravenous routes and little or no protection by the intracerebral, intranasal, or corneal routes. Diminution of interferon production thus appears to be one of the factors for the lowered resistance against herpesvirus infection following certain types of tissue injury.This investigation was supported by research grant (AI-05612) from National Institute of Allergy and Infectious Diseases, U.S. Public Health Service, Bethesda, Md., U.S.A.     

Recovery from herpes simplex virus type-1 hepatitis in a female adult

Summary A study of one case of herpes simplex hepatitis in an adult woman is presented. The clinical feature and laboratory findings were typical for acute hepatitis in a febrile patient without herpetic mucocutaneous lesions. The evidence of high IgM antibody titer in serum against herpes simplex virus and confirmation of the herpes simplex virus hepatitis by immunofluorescent microscopy after liver biopsy helped us establish the diagnosis. After 3-months the patient recovered.Abbreviations HSV Herpes simplex virus - CMV Cytomegalovirus - EBV Epstein Barr virus     

Herpetic retinitis

This paper provides an appreciation of the various forms and consequences of retinal inflammation caused by human herpesviruses. Herpes simplex virus types 1 and 2, varicella zoster virus, cytomegalovirus and Epstein-Barr virus are known to cause retinitis. The prognosis of herpetic retinitis remains poor because it is associated with a high incidence of complications, both during and after the acute disease phase. On diagnosis of retinal necrosis, antiviral treatment must be started promptly to limit disease progression; following this, prophylactic maintenance therapy may be required.     

Comparison of effects of adjuvants on efficacy of virion envelope herpes simplex virus vaccine against labial infection of BALB/c mice.

A subunit virion envelope vaccine of herpes simplex virus type 1 was evaluated for its ability to protect labially infected mice from development of the primary herpetic lesion, encephalitic death, and latent virus infection in the trigeminal ganglion. Several adjuvants, including aluminum hydroxide and polyriboinosinic acid-polyribocytidylic acid complexed with poly-L-lysine and carboxymethyl cellulose were investigated for their ability to enhance protection of the subunit vaccine and were compared in effectiveness with complete Freund adjuvant. The subunit vaccine was demonstrated to be immunogenic, as shown by development of antibody detectable by an enzyme-linked immunosorbent assay. The humoral immune response was correlated with protection from herpetic encephalitis and, at a lower degree, with prevention of the appearance of primary herpetic lesions and acceleration of lesion resolution. The efficacy of the vaccine was most apparent in protecting mice from encephalitic death. To reduce or prevent the development of latent infection was most difficult, but was achieved with some vaccine regimens. Repeated administrations of vaccine with adjuvant were required for this protection. The most effective adjuvant was complete Freund adjuvant, but several synthetic adjuvants were effective, particularly aluminum hydroxide and the polyriboinosinic-polyribocytidylic acid-poly-L-lysine-carboxymethyl cellulose immunoadjuvant.     

Ultrastructural characteristics of a focus of recurrent infection in genital herpes patients (clinical and electron microscopy studies)

In patients with recurrent genital herpes in the active stage of herpetic infection, herpes simplex virus (HSV) is located both extra- and intracellularly in keratinocytes of the pricky and glandular layers of the epidermis as well as in macrophages and neutrophilic leukocytes. The observed incompleted phagocytosis of HSV by macrophages may be one of the causes of insufficient local resistance to the virus.     

Comparison of the sensitivity of a 24 h-shell vial assay, and conventional tube culture, in the isolation of Herpes simplex virus - 1 from corneal scrapings

BACKGROUND: Herpes simplex keratitis is a sight threatening ocular infection. A rapid and specific diagnosis is essential for the institution of specific antiviral therapy and to avoid complications that can arise from misdiagnosis and inappropriate treatment. Though a variety of techniques are available, isolation of Herpes simplex virus 1 (HSV-1) in culture provides the most reliable and specific method, and is considered as the gold standard in laboratory diagnosis of herpes simplex keratitis. We report a comparative study of the sensitivity of a 24 h-shell vial assay and conventional tube culture in the isolation of HSV-1 from corneal scrapings. METHODS: A total of 74 corneal scrapings obtained from 74 patients with a clinical suspicion of herpes simplex keratitis submitted for the isolation of HSV-1, were simultaneously inoculated into shell vial and tube cultures employing the vero cell line. Shell vial and tube cultures were terminated at 24 h and fifth day respectively. Isolation of HSV-1 was confirmed employing an indirect immunofluorescence assay. RESULTS: HSV-1 was isolated from 24/74 (32.4%) specimens employing both the methods. Sensitivity of both the techniques were found to be similar (20/24, 83.3%) (P = 1.0). CONCLUSION: A 24 h-shell vial assay is a rapid alternative technique in comparison to the time consuming conventional tube cultures for the isolation of HSV-1, especially from corneal scrapings for the laboratory diagnosis of herpes simplex keratitis.     

单克隆抗体作单纯疱疹病毒糖蛋白的特性鉴定以及临床应用

应用本室制备的8株抗单纯疱疹病毒糖蛋白单克隆抗体(抗HSV McAb)进行了系列研究,①鉴定出一种新的HSV糖蛋白g30K、gC的一种新形式,以及gC和gD;②建立了HSV感染的临床标本作抗原抗体分型检测的McAb-ELISA双夹心法,检测961份标本效果良好,并己在全国各地一些医疗单位推广使用;③证明McAb治疗家兔实验性单纯疱疹性角膜炎(HSK)有显著效果,并探讨其治疗机理主要为中和作用和ADCC效应;④对部分志愿者用McAb治疗单纯疱疹性角膜炎、妇女生殖器疱疹和小儿口腔疱疹性糜烂,取得明显疗效。     

New approaches to the therapy of HSV infections

Two recent studies have demonstrated single-day regimens of high-dose antiviral therapy (famciclovir 1000 mg twice daily for genital herpes, and famciclovir 1500 mg single dose for herpes labialis) to be effective episodic treatment strategies. Both have the potential to improve patient compliance and therapeutic satisfaction. Patient-initiated episodic therapy (PIE) regimens such as these may improve the time to treatment initiation, which can halt lesion development: PIE allows antiviral drugs to be administered in the narrow therapeutic window that occurs early in the course of a herpes simplex virus (HSV) infection episode. This review article discusses short-course antiviral therapy, which may offer an effective alternative to traditional episodic or suppressive antiviral regimens for HSV-related disease outbreaks.     

Neonatal HSV infection Part I: continuing challenges

Neonatal herpes still presents diagnostic and management problems in view of continuing high mortality and morbidity rates, even though effective antiviral therapy is now available. This article, which reviews current knowledge and progress, provides practical guidelines for the diagnosis, management and treatment of neonatal herpes, based on the literature and decades of experience. It is advisable to focus at the local level on detecting maternal cervical infection, applying the available diagnostic tools and obtaining appropriate medical specialty consultations, as well as improving health worker and patient education about detecting and managing herpes simplex virus infections.