Disodium Phosphonoacetate in Cream Base as a Possible Topical Treatment for Skin Lesions of Herpes Simplex Virus in Cebus Monkeys

Background Postherpetic neuralgia is pain that persists long after the disappearance of the cutaneous lesions of herpes zoster. However, the mechanisms of this delayed pain are unclear. Herpes simplex virus infection induces cutaneous lesions and pain-related responses in mice. The authors examined whether such responses would persist after the disappearance of the cutaneous lesions and whether some analgesics would be effective against them. Methods Female BALB/c mice were inoculated with herpes simplex virus type 1 on the unilateral hind paw. Pain-related responses of hind paw were determined using von Frey filaments. Beginning 5 days after inoculation, mice were given perorally the antiherpes agent acyclovir five times a day for 7 days. Effects of morphine (3-5 mg/kg subcutaneously), gabapentin (30-100 mg/kg perorally), mexiletine (10-30 mg/kg intraperitoneally), and diclofenac (30 mg/kg intraperitoneally) on pain-related responses were examined on days 25-35 after inoculation. Results Viral inoculation induced cutaneous lesions and pain-related responses beginning on day 5 after inoculation. Acyclovir treatment healed all skin lesions by day 15 after inoculation. Approximately half of the mice given acyclovir showed pain-related responses at least until day 40 after inoculation. Morphine, gabapentin, and mexiletine dose-dependently inhibited pain-related responses, but diclofenac had no effects. Conclusions The authors show a mouse model of delayed postherpetic pain. This may be useful for manifesting the mechanisms of postherpetic neuralgia and the factors contributing to the transition from acute herpetic pain to delayed postherpetic pain. This may also be useful for the development of new analgesics against postherpetic neuralgia.

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Herpes Simplex Virus Type 1 Corneal Infection Results in Periocular Disease by Zosteriform Spread

Journal of Virology ◽

10.1128/jvi.75.11.5069-5075.2001 ◽

2001 ◽

Vol 75 (11) ◽

pp. 5069-5075 ◽

Cited By ~ 47

Author(s):

Bretton C. Summers ◽

Todd P. Margolis ◽

David A. Leib

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Skin Lesions ◽

Ocular Infection ◽

Trigeminal Ganglia ◽

Corneal Infection ◽

Recombinant Viruses ◽

Viral Spread ◽

Reporter Activity ◽

Simplex Virus

ABSTRACT In humans and animal models of herpes simplex virus infection, zosteriform skin lesions have been described which result from anterograde spread of the virus following invasion of the nervous system. Such routes of viral spread have not been fully examined following corneal infection, and the possible pathologic consequences of such spread are unknown. To investigate this, recombinant viruses expressing reporter genes were generated to quantify and correlate gene expression with replication in eyes, trigeminal ganglia, and periocular tissue. Reporter activity peaked in eyes 24 h postinfection and rapidly fell to background levels by 48 h despite the continued presence of viral titers. Reporter activity rose in the trigeminal ganglia at 60 h and peaked at 72 h, concomitant with the appearance and persistence of infectious virus. Virus was present in the periocular skin from 24 h despite the lack of significant reporter activity until 84 h postinfection. This detection of reporter activity was followed by the onset of periocular disease on day 4. Corneal infection with a thymidine kinase-deleted reporter virus displayed a similar profile of reporter activity and viral titer in the eyes, but little or no detectable activity was observed in trigeminal ganglia or periocular tissue. In addition, no periocular disease symptoms were observed. These findings demonstrate that viral infection of periocular tissue and subsequent disease development occurs by zosteriform spread from the cornea to the periocular tissue via the trigeminal ganglion rather than by direct spread from cornea to the periocular skin. Furthermore, clinical evidence is discussed suggesting that a similar mode of spreading and disease occurs in humans following primary ocular infection.

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The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane

mBio ◽

10.1128/mbio.01268-17 ◽

2017 ◽

Vol 8 (4) ◽

Cited By ~ 22

Author(s):

Juan Fontana ◽

Doina Atanasiu ◽

Wan Ting Saw ◽

John R. Gallagher ◽

Reagan G. Cox ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Fusion Protein ◽

Surface Protein ◽

Skin Lesions ◽

Enveloped Viruses ◽

Host Membrane ◽

Simplex Virus ◽

Viral Surface Protein ◽

Viral Surface

ABSTRACTAll enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity.IMPORTANCEThe herpesvirus family includes herpes simplex virus (HSV) and other human viruses that cause lifelong infections and a variety of diseases, like skin lesions, encephalitis, and cancers. As enveloped viruses, herpesviruses must fuse their envelope with the host membrane to start an infection. This process is mediated by a viral surface protein that transitions from an initial conformation (prefusion) to a final, more stable, conformation (postfusion). However, the prefusion conformation of the herpesvirus fusion protein (gB) is poorly understood. To elucidate the structure of the prefusion conformation of HSV type 1 gB, we have employed cryo-electron microscopy to study gB molecules expressed on the surface of vesicles. Using different approaches to label gB’s domains allowed us to model the structures of the prefusion and intermediate conformations of gB. Overall, our findings enhance our understanding of HSV fusion and lay the groundwork for the development of new ways to prevent and block HSV infection.

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In VivoAnti-Herpes Simplex Virus Activity of a Sulfated Derivative of Agaricus brasiliensis Mycelial Polysaccharide

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02250-12 ◽

2013 ◽

Vol 57 (6) ◽

pp. 2541-2549 ◽

Cited By ~ 23

Author(s):

F. T. G. S. Cardozo ◽

I. V. Larsen ◽

E. V. Carballo ◽

G. Jose ◽

R. A. Stern ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Sexual Transmission ◽

Skin Lesions ◽

Content Type ◽

Agaricus Brasiliensis ◽

Infection Models ◽

Spread F ◽

Simplex Virus ◽

Viral Titers

ABSTRACTAgaricus brasiliensis(syn.A. subrufescens), a basidiomycete fungus native to the Atlantic forest in Brazil, contains cell walls rich in glucomannan polysaccharides. The β-(1→2)-gluco-β-(1→3)-mannan was isolated fromA. brasiliensismycelium, chemically modified by sulfation, and named MI-S. MI-S has multiple mechanisms of action, including inhibition of herpes simplex virus (HSV) attachment, entry, and cell-to-cell spread (F. T. G. S. Cardozo, C. M. Camelini, A. Mascarello, M. J. Rossi, R. J. Nunes, C. R. Barardi, M. M. de Mendonça, and C. M. O. Simões, Antiviral Res. 92:108–114, 2011). The antiherpetic efficacy of MI-S was assessed in murine ocular, cutaneous, and genital infection models of HSV. Groups of 10 mice were infected with HSV-1 (strain KOS) or HSV-2 (strain 333). MI-S was given either topically or by oral gavage under various pre- and posttreatment regimens, and the severity of disease and viral titers in ocular and vaginal samples were determined. No toxicity was observed in the uninfected groups treated with MI-S. The topical and oral treatments with MI-S were not effective in reducing ocular disease. Topical application of MI-S on skin lesions was also not effective, but cutaneously infected mice treated orally with MI-S had significantly reduced disease scores (P< 0.05) after day 9, suggesting that healing was accelerated. Vaginal administration of MI-S 20 min before viral challenge reduced the mean disease scores on days 5 to 9 (P< 0.05), viral titers on day 1 (P< 0.05), and mortality (P< 0.0001) in comparison to the control groups (untreated and vehicle treated). These results show that MI-S may be useful as an oral agent to reduce the severity of HSV cutaneous and mucosal lesions and, more importantly, as a microbicide to block sexual transmission of HSV-2 genital infections.

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Microemulsion-Based Oxyresveratrol for Topical Treatment of Herpes Simplex Virus (HSV) Infection: Physicochemical Properties and Efficacy in Cutaneous HSV-1 Infection in Mice

AAPS PharmSciTech ◽

10.1208/s12249-012-9828-x ◽

2012 ◽

Vol 13 (4) ◽

pp. 1266-1275 ◽

Cited By ~ 18

Author(s):

Pattaraporn Sasivimolphan ◽

Vimolmas Lipipun ◽

Garnpimol Ritthidej ◽

Khanidtha Chitphet ◽

Yoshihiro Yoshida ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Physicochemical Properties ◽

Topical Treatment ◽

Simplex Virus ◽

Hsv 1

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Multi-organ involvement secondary to varicella zoster virus, herpes simplex virus and cytomegalovirus in an immunocompromised patient

BMJ Case Reports ◽

10.1136/bcr-2018-228150 ◽

2019 ◽

Vol 12 (3) ◽

pp. e228150 ◽

Cited By ~ 1

Author(s):

Ripal Jariwala ◽

Kristen Zeitler ◽

Nicole D Riddle ◽

Chakrapol Sriaroon

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Varicella Zoster Virus ◽

Immunocompromised Patient ◽

Case Reports ◽

Skin Lesions ◽

Viral Reactivation ◽

Organ Involvement ◽

Varicella Zoster ◽

Simplex Virus

The use of immunosuppressing agents can act as a catalyst for viral reactivation, promoting systemic infection with organ involvement. Current literature remains sparse on this topic but does provide individual case reports involving single viruses. We present the case of an immunocompromised patient with skin lesions, pancreatitis, colitis and hepatitis. Work-up revealed varicella zoster virus, which likely put the patient at risk for multi-organ involvement, as well as clinical suspicion of other implicated viruses, specifically herpes simplex virus and cytomegalovirus. A high clinical index of suspicion along with biopsy guidance for viral involvement in immunocompromised patients is crucial for early diagnosis and treatment of these conditions.

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Topical treatment of recurrent genital herpes simplex virus infections with trisodium phosphonoformate (foscarnet): double blind, placebo controlled, multicentre study.

Sexually Transmitted Infections ◽

10.1136/sti.62.4.247 ◽

1986 ◽

Vol 62 (4) ◽

pp. 247-250

Author(s):

S E Barton ◽

P E Munday ◽

G R Kinghorn ◽

W I van der Meijden ◽

E Stolz ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Multicentre Study ◽

Genital Herpes ◽

Topical Treatment ◽

Virus Infections ◽

Recurrent Genital Herpes ◽

Double Blind ◽

Double Blind Placebo ◽

Simplex Virus

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Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses

Virus Evolution ◽

10.1093/ve/veaa012 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Florent Lassalle ◽

Mathew A Beale ◽

Tehmina Bharucha ◽

Charlotte A Williams ◽

Rachel J Williams ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Direct Sequencing ◽

Clinical Manifestations ◽

Skin Lesions ◽

Target Enrichment ◽

Mortality And Morbidity ◽

Simplex Virus ◽

Hsv 1

Abstract Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70 per cent of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. In contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.

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Efficacy ofBidens pilosaExtract against Herpes Simplex Virus InfectionIn VitroandIn Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/413453 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Shinji Nakama ◽

Kazumi Tamaki ◽

Chie Ishikawa ◽

Masayuki Tadano ◽

Naoki Mori

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Skin Lesions ◽

Host Cells ◽

Raw 264.7 Cells ◽

Bidens Pilosa ◽

Culture Cells ◽

Medical Plant ◽

Simplex Virus ◽

Hsv 1

The development of strains of herpes simplex virus (HSV) resistant to drugs has been reported among the immunocompromised patients. Thus, there is a need to develop new therapeutic agents for HSV infections. We evaluated the anti-HSV activity ofBidens pilosa(B. pilosa), a tropical weed, in tissue culture cells and a mouse model.B. pilosaextract showed potent virucidal activity. It inhibited plaque formation and suppressed virus yield in Vero and RAW 264.7 cells infected with HSV-1 and HSV-2. Both the binding of virus to host cells and penetration of virus into cells were also blocked byB. pilosa. Furthermore,B. pilosawas effective against thymidine kinase-deficient and phosphonoacetate-resistant HSV-1 strains.B. pilosatreatment increased the survival rate of HSV-infected mice and limited the development of skin lesions. Our results indicate thatB. pilosahas anti-HSV activity and is thus a potentially useful medical plant for treatment of HSV infection.

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