A Cationic TAT Peptide Inhibits Herpes Simplex Virus Type 1 Infection of Human Corneal Epithelial Cells

Larsen, Inna V.; Brandt, Curtis R.

doi:10.1089/jop.2010.0076

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…The antiviral activity of TAT-Cd 0 is not cell type dependent, and the peptide has been shown to have low cytotoxicity in culture and in a murine eye model. 15,16 TAT-Cd 0 also inactivates virus in solution (EC 50 ¼ 34 lM) and treatment of cells prior to infection can make them resistant to infection (EC 50 ¼ 0.4 lM). 14 Based on these properties, TAT-Cd 0 has the potential to be an effective antiviral with alternative mechanisms of action compared with currently available drugs.…”

Section: Results Tat-cdmentioning

confidence: 99%

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Jose¹,

Larsen

Gauger

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To test the in vivo activity of a peptide derived from the protein transducing domain of the human immunodeficiency virus (HIV) Tat protein, TAT-Cd 0 , in a murine herpes simplex type 1 (HSV-1) keratitis model. METHODS.The efficacy of TAT-Cd 0 was assessed in a postinfection treatment model with different concentrations (1 mg/mL, 0.1 mg/mL, 0.01 mg/mL) of the peptide in one of four delivery vehicles: artificial tears, PBS, methylcellulose, and aquaphor cream. Treatment began within 4 or 24 hours postinfection. Viral titers in the tear film were determined by plaque assay. RESULTS. TAT-Cd0 reduced the severity of keratitis in all of the delivery vehicles tested when treatment started, 4 hours postinfection. Peptide in the tears or PBS delivery vehicle had the most significant reduction in disease severity and delayed the onset of vascularization and stromal keratitis. The percentage of mice presenting with disease was also significantly reduced and viral titers were reduced by 1 log at 24 hours postinfection in mice treated with 1 mg/mL TAT-Cd 0 , suggesting that inhibiting replication early is sufficient to achieve clinical effects. Lower concentrations were not effective and delaying treatment by 24 hours was also not effective.CONCLUSIONS. This study shows that TAT-Cd 0 is an effective antiviral against HSV-1 strain KOS when applied shortly postinfection and that aqueous-based formulations are more suitable. (Invest Ophthalmol Vis Sci.

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Section: Results Tat-cdmentioning

confidence: 99%

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Jose¹,

Larsen

Gauger

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…148 A cationic steroid antibiotic (CSA)-13 that is proposed to mimic the activity of endogenous AMPs can inhibit Acanthamoeba trophozoite growth without significant toxicity to mouse fibroblast cells. 219 The cationic Peptide TAT-Cd0 can reduce the ability of HSV-1 to infect human corneal epithelial cells 220 and reduce the severity of keratitis, delay the onset of vascularisation and stromal keratitis, reduce the percentage of mice presenting with disease and viral titres. 221 However, treatment needed to be early in the disease process (four hours after initiation of infection) for these effects to be seen.…”

Section: Evidence For Effectiveness Of Antimicrobial Peptides To Treat Ocular Infectionsmentioning

confidence: 99%

Antimicrobial resistance of ocular microbes and the role of antimicrobial peptides

Tummanapalli

Willcox

2021

Clinical and Experimental Optometry

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Isolation of antimicrobial-resistant microbes from ocular infections may be becoming more frequent. Infections caused by these microbes can be difficult to treat and lead to poor outcomes. However, new therapies are being developed which may help improve clinical outcomes. This review examines recent reports on the isolation of antibiotic-resistant microbes from ocular infections. In addition, an overview of the development of some new antibiotic therapies is given. The recent literature regarding antibiotic use and resistance, isolation of antibiotic-resistant microbes from ocular infections and the development of potential new antibiotics that can be used to treat these infections was reviewed. Ocular microbial infections are a global public health issue as they can result in vision loss which compromises quality of life. Approximately 70 per cent of ocular infections are caused by bacteria including Chlamydia trachomatis, Staphylococcus aureus, and Pseudomonas aeruginosa and fungi such as Candida albicans, Aspergillus spp. and Fusarium spp. Resistance to first-line antibiotics such as fluoroquinolones and azoles has increased, with resistance of S. aureus isolates from the USA to fluoroquinolones reaching 32 per cent of isolates and 35 per cent being methicillin-resistant (MRSA). Lower levels of MRSA (seven per cent) were isolated by an Australian study. Antimicrobial peptides, which are broad-spectrum alternatives to antibiotics, have been tested as possible new drugs. Several have shown promise in animal models of keratitis, especially treating P. aeruginosa, S. aureus or C. albicans infections. Reports of increasing resistance of ocular isolates to mainstay antibiotics are a concern, and there is evidence that for ocular surface disease this resistance translates into worse clinical outcomes. New antibiotics are being developed, but not by large pharmaceutical companies and mostly in university research laboratories and smaller biotech companies. Antimicrobial peptides show promise in treating keratitis.

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“…They are being synthesized and used as inhibitors against HSV infections 127 . The TAT (transactivator of transcription)-peptide, derived from HIV, has been shown to inhibit infection of HSV in the in vitro and in vivo models of HSV infections 128 129 . A study showed the effect of a synthetic 3-OS HS specific peptide: G2 in blocking HSV-2 infections in human cervical (HeLa) cell lines.…”

Section: Treatment and Preventionmentioning

confidence: 99%

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

Jaishankar

Shukla

2016

MIC

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Etiology, transmission and protection: Herpes simplex virus-2 (HSV-2) is a leading cause of sexually transmitted infections with recurring manifestations throughout the lifetime of infected hosts. Currently no effective vaccines or prophylactics exist that provide complete protection or immunity from the virus, which is endemic throughout the world. Pathology/Symptomatology: Primary and recurrent infections result in lesions and inflammation around the genital area and the latter accounts for majority of genital herpes instances. Immunocompromised patients including neonates are susceptible to additional systemic infections including debilitating consequences of nervous system inflammation. Epidemiology, incidence and prevalence: More than 500 million people are infected worldwide and most reported cases involve the age groups between 16-40 years, which coincides with an increase in sexual activity among this age group. While these numbers are an estimate, the actual numbers may be underestimated as many people are asymptomatic or do not report the symptoms. Treatment and curability: Currently prescribed medications, mostly nucleoside analogs, only reduce the symptoms caused by an active infection, but do not eliminate the virus or reduce latency. Therefore, no cure exists against genital herpes and infected patients suffer from periodic recurrences of disease symptoms for their entire lives. Molecular mechanisms of infection: The last few decades have generated many new advances in our understanding of the mechanisms that drive HSV infection. The viral entry receptors such as nectin-1 and HVEM have been identified, cytoskeletal signaling and membrane structures such as filopodia have been directly implicated in viral entry, host motor proteins and their viral ligands have been shown to facilitate capsid transport and many host and HSV proteins have been identified that help with viral replication and pathogenesis. New understanding has emerged on the role of autophagy and other innate immune mechanisms that are subverted to enhance HSV pathogenesis. This review summarizes our current understanding of HSV-2 and associated diseases and available or upcoming new treatments.

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A Cationic TAT Peptide Inhibits Herpes Simplex Virus Type 1 Infection of Human Corneal Epithelial Cells

Cited by 4 publications

References 22 publications

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Antimicrobial resistance of ocular microbes and the role of antimicrobial peptides

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

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A Cationic TAT Peptide Inhibits Herpes Simplex Virus Type 1 Infection of Human Corneal Epithelial Cells

Cited by 4 publications

References 22 publications

A Cationic Peptide, TAT-Cd0, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

A Cationic Peptide, TAT-Cd0, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

Antimicrobial resistance of ocular microbes and the role of antimicrobial peptides

Genital Herpes: Insights into Sexually Transmitted Infectious Disease

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Product

Resources

About

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo

A Cationic Peptide, TAT-Cd⁰, Inhibits Herpes Simplex Virus Type 1 Ocular Infection In Vivo