Herpes simplex keratitis:A brief clinical overview

The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the cornea.One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea.After the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the eye.The virus may remain dormant for extended periods.Periodic reactivation of the virus can occur,leading to recurrent episodes of HSK.Factors triggering reactivation include stress,illness,immunosuppression,or trauma.Recurrent episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial disease.The severity and frequency of recurrences vary among individuals.Severe cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme cases.The cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual impairment.The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization.Antiviral medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for prophylaxis.The immune response to the virus can contribute to corneal damage.Inflammation,caused by the body's attempt to control the infection,may inadvertently harm the corneal tissues.Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation.In summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

Interleukin 1βreceptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Black Garlic as an Antiviral for Herpes Simplex Virus-2 in Lung Cells

Allicin, an antioxidant, is known for providing garlic with its unique fragrance and taste, as well as for its antimicrobial properties. Black garlic, a fermented form of garlic, contains higher levels of antioxidants than fresh garlic. Antioxidants play a vital role in alleviating cellular stress during viral infections. Viral infections result in oxidative stress through the production of reactive oxidative species (ROS). A prolonged state of oxidative stress can result in cell death, DNA damage, and disease progression. In this study, black garlic extract (BGE) is evaluated for its ability to mitigate cytopathic effects and oxidative stress caused by herpes simplex virus-2 (HSV-2) infections in vitro. Antiviral assays were performed to determine the percent of viral inhibition resulting from treatment with the BGE. ROS-GloTM H2O2 assays were then completed to measure the post-infection ROS levels of BGE-treated virus and cells. The results thus far suggest that BGE may inhibit viral infection and decrease levels of oxidative stress.

Autoimmune complications and clinical outcomes of herpes simplex encephalitis in children: A case series

Objective:To report the neurologic prognosis and autoimmune complications of 16 cases of childhood herpes simplex virus encephalitis.Methods:The study was conducted atŞanlıurfa Training and Research Hospital,Turkey from June 2017 to August 2019.The study included 16 pediatric patients aged between 6 months and 17 years(median age 77.7 months)who were diagnosed with herpes simplex virus type 1 encephalitis by pediatric infectious disease and pediatric neurology clinics.Patients were followed using patient records,and interviews at the pediatric neurology clinic or via the telephone.Clinical and demographic data,received therapies,neurologic prognosis and complications were evaluated.Results:Patients with and without autoimmune encephalitis were compared in terms of age,sex,symptom duration before treatment,initial cerebrospinal fluid protein,glucose,red blood count and white blood count but no significant difference was found.Autoimmune complications were seen in four patients.N-methyl-D-aspartate encephalitis was observed in three patients and choreoathetosis was seen in one patient.The average follow-up period was 48.3 months.Twenty-five percent of the patients were receiving multiple antiepileptic drug(AED)treatment,43.8%were receiving single AED treatment and 31.3%were not receiving AED treatment at the end of the follow-up.Motor disability was observed in 12.5%and drug-resistant epilepsy was observed in 6.3%who had autoimmune complications.Conclusions:Seizures and movement disorders were controlled with immunotherapy and autoantibodies should be studied routinely.Treatment should be started early upon recognition of autoimmune complications through follow-up by measuring autoantibody levels and clinical examination results.Effective prevention and curative treatment modalities are needed to avoid herpes simplex virus encephalitis complications.

Antiviral activity of mangiferin from the rhizome of Anemarrhena asphodeloides against herpes simplex virus type 1

Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.

Streptococcus pneumoniae and Herpes Simplex Virus-1 Central Nervous System Co-Infection

Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is well described but most cases are related to oral or cutaneous lesions or in respiratory samples. HSV-1 CNS reactivation after Streptococcus pneumoniae meningitis is a very rare event and may have significant morbidity and mortality. In this case report, we describe a 71-year-old female patient that presented with a history of abdominal pain and confusion/disorientation that had tonic-clonic seizures while in the Emergency Department. The diagnostic work-up confirmed CNS co-infection caused by Streptococcus pneumoniae and HSV-1. Of note, beyond age, the patient had no known risk factors for both entities and recovered fully after antibiotic and antiviral therapy. This case underlines that clinicians must be aware of CNS co-infection despite being a rare diagnosis. This should be suspected particularly in patients who present an unusual clinical course of CNS infection.

A Meta-Analysis on the Correlation Between Herpes Simplex Virus Type II Infection and Adverse Pregnancy Outcomes in China

Objective:To systematically evaluate the relationship between herpes simplex virus type II(HSV-2)infection in pregnant women and the adverse pregnancy outcomes(preterm delivery,spontaneous abortion,stillbirth,monstrum,low birth weight,intrauterine growth retardation,premature rupture of membranes),so as to provide clinical guidance for the prevention and treatment of adverse pregnancy outcomes caused by HSV-2 infection in pregnant women.Methods:2140 articles were collected from PubMed,China National Knowledge Infrastructure(CNKI),and other databases for the past 20 years.According to the inclusion criteria,the literatures about the relationship between HSV-2 infection of pregnant women and adverse pregnancy outcomes were screened.The effect model was determined by heterogeneity test results,and the meta-analysis was carried out by RevMan 5.3 software.Results:The results of meta-analysis showed that the positive rate of HSV-2 was higher in the adverse pregnancy group than in the control group(odds ratio[OR]:7.92,95%confidence interval[Cl]:3.91-16.01),and the difference was statistically significant.Conclusion:HSV-2 infection will increase the risk of adverse pregnancy outcomes.Prevention and effective control of HSV-2 infection in early pregnancy can reduce the rate of adverse pregnancy outcome,which is of great significance to the promotion of eugenics.

Oral and perioral herpes simplex virus infection type I in a fivemonth- old infant: A case report

BACKGROUND Herpes simplex virus(HSV)is a highly infectious pathogen that is easily transmitted via the bodily fluids of an infected individual.This virus usually affects individuals older than six months of age,and rarely causes lesions or symptoms in younger patients.CASE SUMMARY We present the case of a five-month-old healthy girl who presented with painful herpetic gingivostomatitis and perioral vesicles.We discuss the pathophysiology of primary HSV infection and the effect of maternal antibodies on the infant’s immune system.In addition,we explain the diagnosis,management,and prognosis of HSV infection in young infants.CONCLUSION This case highlights the importance of early diagnosis and management of HSV infections to decrease the risk of developing severe complications and death.

Oncolytic Engineering of ICP34.5 and LAT of Herpes Simplex Virus Type 1

Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.

New strategies against drug resistance to herpes simplex virus

Herpes simplex virus （HSV）, a member of the Herpesviridae family, is a significant human pathogen that results in mucocutaneous lesions in the oral cavity or genital infections. Acyclovir （ACV） and related nucleoside analogues can successfully treat HSV infections, but the emergence of drug resistance to ACV has created a barrier for the treatment of HSV infections, especially in immunocompromised patients. There is an urgent need to explore new and effective tactics to circumvent drug resistance to HSV. This review summarises the current strategies in the development of new targets （the DNA helicase/primase （H/P） complex）, new types of molecules （nature products） and new antiviral mechanisms （lethal mutagenesis of Janus-type nucleosides） to fight the drug resistance of HSV.

Herpes simplex virus-1 infection or Simian virus 40-mediated immortalization of corneal cells causes permanent translocation of NLRP3 to the nuclei

AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.

Asymptomatic seminal infection of herpes simplex virus:impact on male infertility

In more than half of infertile men, the cause of their infertility is unknown. Several studies revealed the role of viral infections in male infertility. The aim of the present study was to determine the prevalence of herpes simplex virus-1 （HSV-1） and HSV-2 in semen from asymptomatic infertile male patients, and its association with altered semen parameters. A total of 70 semen samples were collected from infertile men who attended the Research and Clinical Center for Infertility in Yazd, Iran. Semen analysis and diagnostic real-time PCR using specific primers and probes for HSV-1 and HSV-2 DNA were performed. Comparison of semen parameters between virally in- fected and non-infected samples were performed with independent t-test and Mann-Whitney test. Semen analysis showed that infertile men fell into two groups, the male factor group and the unexplained group. HSV-1 and HSV-2 DNA was detected in 16 （22.9%） and 10 （14.3%） of 70 semen samples, respectively. All HSV-positive samples had abnormal semen parameters （the male factor group）. Although HSV infection was not associated with sperm motility and morphological defects, it was correlated with lower sperm count in the seminal fluid. The findings suggest that asymptomatic seminal infection of HSV plays an important role in male infertility by adversely af- fecting sperm count.

Contributions of neurotropic human herpesviruses herpes simplex virus 1 and human herpesvirus 6 to neurodegenerative disease pathology

Human herpesviruses （HVs） have developed ingenious mechanisms that enable them to traverse the defenses of the central nervous system （CNS）. The ability of HVs to enter a state of latency, a defining char- acteristic of this viral family, allows them to persist in the human host indefinitely. As such, HVs represent the most frequently detected pathogens in the brain. Under constant immune pressure, these infections are largely asymptomatic in healthy hosts. However, many neurotropic HVs have been directly connected with CNS pathology in the context of other stressors and genetic risk factors. In this review, we discuss the potential mechanisms by which neurotropic HVs contribute to neurodegenerative disease （NDD） patholo- gy by highlighting two prominent members of the HV family, herpes simplex virus 1 （HSV-1） and human herpesvirus 6 （HHV-6）. We （i） introduce the infectious pathways and replicative cycles of HSV-1 and HHV-6 and then （ii） review the clinical evidence supporting associations between these viruses and the NDDs Alzheimer＇s disease （AD） and multiple sclerosis （MS）, respectively. We then （iii） highlight and dis- cuss potential mechanisms by which these viruses exert negative effects on neurons and glia. Finally, we （iv） discuss how these viruses could interact with other disease-modifying factors to contribute to the initiation and/or progression of NDDs.

A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes

Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.

Expression of Cytokines IL-2, IL-10 and TNF-α in Mice with Herpes Simplex Viral Encephalitis

The expression of the cytokines IL-2, IL-10, TNF-α and their roles in mice with herpes simplex viral encephalitis （HSE） were studied. By using semiquantitative reverse transcription polymerase chain reaction （RT-PCR）, the expressions of IL-2, IL-10 and TNF-α mRNA in control group, HSE group and acyclovir （ACV）-treated group were detected and the pathological changes of brain were observed. It was found that after HSV1 infection, the cerebral lesions of haemorrhage and necrosis in mice were observed under the microscopy, and the levels of IL-2, IL-10 and TNF-α were increased remarkably. After treatment with ACV after HSV1 infection, the cerebral lesions in mice were improved, the level of IL-2 maintained stable, IL-10 was increased consistently, and TNF-α was decreased significantly as compared with those in HSE group. In acute HSE, many cytokines are upregulated, including IL-2, IL-10 and TNF-α to eliminate virus and TH1 type response is dominant. In convalescence, there is a shift in the cytokine expression profile from TH1 profile to TH2 profile and the shift can inhibit the overexpression of immune response in animals. ACV has remarkable effects in the treatment of HSE.

DNA vaccine expressing herpes simplex virus 1 glycoprotein C and D protects mice against herpes simplex keratitis

AIM： To investigate whether DNA vaccine encoding herpes simplex virus 1（HSV-1） glycoprotein C（g C） and glycoprotein D（g D） will achieve better protective effect against herpes simplex keratitis（HSK） than DNA vaccine encoding gD alone. METHODS： DNA vaccine expressing gD or gC combined g D（g D.g C） were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293 T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2 wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS： Fusion protein g D.g C could be expressed successfully in cultured 293 T cells. And, p RSC-g C.g DIL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and s Ig A production, enhanced cytotoxicities of splenocytes and nature killer cells（NK）,when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION： gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.

Infection and Immunity of Herpes Simplex Virusin the Culture System sof Lym phocytes and Monocyte-Macrophages

The study was made by the method of experimental infection using cultured cells in vitro. The characteristic of HSV infection of the cells and the effects of immunity factors on the infection were analyzed by cytopathic effect, double antibodies sandwich ELISA for immunoglobulin yield, hemolytic plaque assay for specific SRBC antibody forming cells, microcytopathy assay for viral titer, IFA for viral antigen and PCR for viral DNA.The results were as follows: ①A series of models of HSV infection were established, including the model of HSV 1 persistent infection of Raji cells, the model of acute and cytocidal HSV 1 infection of HSB\-2 cells, the models of temporary persistent HSV 1 infection of LPS stimulated U\-\{937\} cells and murine peritoneal macrophages and the models of inhibitions both of IgG synthesis and specific SRBC antibody production by HSV 1 infection of human tonsillar lymphocytes activated by PWM stimulating. ②According to the characteristic of HSV infection of lymphocyte and monocyte macrophage, it was reasonable that stimulating with antigen, mitogen, LPS, or inflammatory factors might make lymphocytes and/or monocyte macrophages become permissive cells of replicative HSV infection, or might activate the latent virus, resulting in HSV dissemination by blood circulation. ③It was proved that IFN α, IFN γ, TNF, M CSF, GM CSF and IL 3 have an inhibitory effect on HSV replication in lymphocyte and monocyte macrophage, respectively and reversed the replicative enhancement activity of LPS, suggesting that applications of these immunity factors favour lymphocytes and monocyte macrophages with a resistance to HSV replicative infection and with an inhibition of latent virus reactivation in vivo, and therefore, it might be helpful for preventing the virus from dissemination by blood circulation.\;

Antiviral Effect of Chinonin against Herpes Simplex Virus

In order to investigate the antiviral effect of chinonin against Herpes simplex virus (HSV), the encephalitis model in mice and skin infection model in guinea pigs were established by HSV-Ⅰ and HSV-Ⅱ infection respectively. Acyclovir was used as the positive reference drug to evaluate the antiviral capacity of chinonin. Chinonin showed an obvious therapeutic effect on encephalitis in mice at doses of 25 and 50 mg/kg. At both dosages, chinonin demonstrated stronger protection than acyclovir (1 and 5 mg/kg) to the infected mice from death. It was also found that chinonin could treat the skin infection in guinea pigs effectively. The therapeutic effect of chinonin was similar to that of acyclovir (5 mg/kg) at 25 mg/kg but obviously better than that at 50 and 75 mg/kg. In conclusion, chinonin is a potential candidate for the treatment against HSV.

Cooperative Therapeutic Effects of Herpes Simplex Virus Thymidine Kinase Gene/Ganciclovir System and Chemotherapeutic Agents on Prostate Cancer in vitro

The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir （HSV-tk/GCV） approach by the addition of several commonly clinical chemotherapeutic agents on hormone refractory prostate cancer （HRPC） cells PC-3m were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA and protein expression of HSV-tk was detected by reverse-transcript polymerase chain reaction （RT-PCR） and strept avidin-biotin complex （SABC） im- munohistochemical method. The killing effect of GCV, cisplatin （CDDP）, etoposide （VP-16）, vincristine （VCR）, methotrexate （MTX）, 5-fluorouracil （5-Fu）, and suramin on PC-3m cells was evaluated by morphological assessment analysis, trypan blue exclusion assay and MTT assay respectively. Additionally, the cooperative effect of HSV-tk/GCV system combined with the above agents on the target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry （FCM）. The results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or suramin led to an enhanced cellular killing effect, but with CDDP resulted in a reduced one and with MTX in an approximate one. FCM revealed that synergistic use of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and necrosis with the apoptosis index being 36.38 % and 35.51%, and the proportion of necrosis being 33.05 % and 28.87 %, respectively. In conclusion, HSV-tk/CGV approach by addition of certain clinical available chemotherapeutic drugs brings on statistically significant enhanced cell killing over single-agent treatment. Our results highlight the potential for such new combination therapies for future treatments of HRPC.

Anti-viral activity of Staphylococcus aureus lysates against herpes simplex virus type-Ⅰinfection:an in vitro and in vivo study

AIM:To investigate the effect of Staphylococcus aureus(S.aures)lysates(SALs)on herpes simplex virus type-Ⅰ(HSV1)infection in human corneal epithelial(HCE)cells and in a mouse model of HSV1 keratitis.METHODS:HCE,Vero,HeLa,and BV2 cells were infected with HSV1[HSV1f strain,HSV1f;HSV-1-H129 with green fluorescent protein(GFP)knock-in,HSV1g].Pre-or post-infection,SAL at various concentrations was added to the culture medium for 24 h.GFP fluorescence in HSV1g or plaque formation by HSV1f were examined.The effects of heat-treated SAL,precooled acetone-precipitated SAL,and SAL subjected to ultrafiltration(100 kDa)were evaluated.The effects of other bacterial components and lysates on HSV1 infection were also tested,including lipoteichoic acid(LTA),peptidoglycan(PGN),staphylococcal protein A(SPA),andα-hemolysin from S.aureus(α-toxin)as well as lysates from a wild-type S.aureus strain,S.epidermidis,and Escherichia coli(W-SAL,SEL,and ECL,respectively).In addition,SAL eye drops were applied topically to BALB/c mice with HSV1 keratitis,followed by in vivo observations.RESULTS:The cytopathic effect,plaque formation(HSV1f),and GFP expression(HSV1g)in infected cells were inhibited by SAL in a dose-dependent manner.The active component of SAL(≥100 kDa)was heat-sensitive and retained activity after acetone precipitation.In HSV1ginfected cells,treatment with LTA-sa,α-toxin,PGN-sa,or SPA did not inhibit GFP expression.SAL,W-SAL,and SEL(but not ECL)decreased GFP expression.In mice with HSV1 keratitis,SAL reduced corneal lesions by 71%.CONCLUSION:The results of this study demonstrate that SAL can be used to inhibit HSV1 infection,particularly keratitis.Further studies are needed to determine the active components and mechanism underlying the effects of SAL.