Herpes Simplex Virus and Human CNS Infections
Sunit K. Singh, Daniel Růžek in Neuroviral Infections, 2013
The exact origin of herpes in humans is unknown. Herpes simplex virus (HSV) causes fever blisters or cold sores around the lips or in the genital area. The disease caused by the virus has been known for thousands of years. The characteristic vesicles were described by the ancient Greeks when Hippocrates documented sores that seemed to “to creep or crawl.” The name of the virus comes from the Greek word herpes referring to the lesions caused by the virus. Astruc, physician to King Louis, was the first to describe herpes genitalis and data describing recurrences of the lesions were published by Unna (1883). In 1873, Vidal (1873) first demonstrated that HSV was infectious. Finally, Gruter isolated HSV in 1924 and showed how it could be transmitted from rabbit to rabbit (Gruter 1924). Later on, Burnet and Williams defined that herpes simplex infections seem to persist in the host when the virus remains lifelong latent, but under the stimulus of trauma, fever may be provoked and result to visible herpetic lesion (Burnet and Williams 1939). Schneweiss demonstrated that, in fact, two serotypes of HSV existed, HSV type 1 (HSV-1) and HSV type 2 (HSV-2) (Schneweiss 1962).
Diagnostic Approach to Fulminant Hepatitis in the Critical Care Unit
Cheston B. Cunha, Burke A. Cunha in Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Herpes simplex virus 1 and 2 (HSV) are double-stranded DNA viruses that belong to the herpesvirus family, Herpesviridae, and can be contracted through direct contact with an active lesion or body fluid of an infected person. The HSV is an uncommon cause of ALF that typically occurs in immunosuppressed patients [3]. The HSV hepatitis accounts for less than 1% of all cases of ALF and carries a mortality rate of 80% secondary to delayed diagnosis [11]. Patients who are male, older than 40 years, immunosuppressed, and/or with other liver diseases are more likely to progress to death and need liver transplantation [12]. Clinical symptoms of HSV infection include fever, anorexia, abdominal pain, leukopenia, and coagulopathy. The absence of mucocutaneous lesions seen in half of patients leads to a high frequency of delayed diagnosis [13]. Laboratory abnormalities include low to normal bilirubin, resulting in anicteric hepatitis, transaminase levels 100- to 1000-fold above baseline (AST > ALT), and a prolonged INR. Diagnosis is made through the detection of antibodies against HSV (IgM and IgG anti-HSV) in serum and confirmatory testing of PCR in blood or tissues [11]. HSV DNA by PCR is the most sensitive test for the diagnosis of HSV hepatitis [14]. Rapid initiation of acyclovir increases the rates of transplant-free survival.
Pathogenesis
Marie Studahl, Paola Cinque, Tomas Bergström in Herpes Simplex Viruses, 2017
Herpes simplex virus-1 (HSV-1) is one of the most thoroughly investigated human viruses, but the number of unanswered questions regarding its pathogenesis and natural course of infection tend to increase with understanding. This chapter reviews some aspects of the pathogenesis of HSV-1 and HSV-2 infections, with emphasis on data derived from humans as hosts and from their viral isolates. An important limitation in the field of HSV pathogenesis is the difficulty in studying asymptomatic infection, which therefore remains enigmatic. As transmission seems to occur commonly during asymptomatic phases, clinical manifestations including mucocutaneous lesions may be regarded as extrapolations of events occurring during a silent, natural infection. In fact, disease events may be unnecessary for the further existence of HSV in the human population, yet they still exist. However, the complications encountered during HSV-1 and HSV-2 infections, thoroughly reviewed in this volume, strongly indicate a need for further defining determinants of pathogenicity, such as viral virulence factors and host susceptibility traits, to improve treatment and prophylaxis.
Severe oral stomatitis due to reactivation of herpes simplex virus type 1 in a methotrexate-treated patient with dermatomyositis
Published in Immunological Medicine, 2021
Takahiko Akagi, Tomoyuki Mukai, Shunichi Fujita, Takenobu Yamamoto, Mikiko Fukuda, Yoshitaka Morita
Methotrexate (MTX) is one of the most widely used immunosuppressive drugs to treat autoimmune diseases. Oral mucositis is a common adverse event associated with MTX. When patients develop stomatitis during MTX treatment, mucosal toxicity of MTX is first considered the cause of stomatitis. Further, several other etiologies need to be considered in the differential diagnosis, including infection (with bacteria, viruses, or fungi), trauma, systemic lupus erythematosus, immunobullous diseases, and recurrent aphthous stomatitis [1,2]. Recurrent herpes simplex virus type 1 (HSV-1) infection, which is caused by virus reactivation, is usually asymptomatic or results in localized vesicular lesions at the mucocutaneous junction of the lips in immunocompetent individuals. In contrast, HSV-1 reactivation can induce severe intraoral stomatitis in immunocompromised patients with human immunodeficiency virus (HIV) infection, undergoing myeloablative conditioning regimens, or receiving intensive immunosuppressive therapy to prevent rejection reactions after organ transplantation [3–5]. Here, we report a case of a patient who developed severe oral stomatitis due to HSV-1 reactivation during immunosuppressive treatment with low-dose MTX for dermatomyositis. This case illustrates the importance of a differential diagnosis for stomatitis during immunosuppressive therapy, especially MTX treatment.
Signal peptide peptidase: a potential therapeutic target for parasitic and viral infections
Published in Expert Opinion on Therapeutic Targets, 2022
Christopher Schwake, Michael Hyon, Athar H. Chishti
The human herpes simplex virus types −1 and −2 (HSV-1/2) cause chronic lifelong infection that are mainly asymptomatic; however, blisters and sores can occur in infected individuals. Furthermore, HSV-1 can cause serious eye infections with risk of blindness. HSV-1 utilizes its envelope protein glycoprotein K (gK) for binding to SPP during infection and this interaction is required for replication (Figure 5D) [78]. No other HSV-1 gene binds to SPP except gK. A later study investigating the involvement of SPP in HSV-1 infection in vivo using an inducible SPP mouse knockout model confirmed gK as a binding partner of SPP [79]. Interestingly, they found that viral latency was also reduced in SPP knockout mice [79]. Pharmacological inhibition of SPP with five small molecule inhibitors including (Z-LL)2-ketone and L685,485 were able to reduce HSV-1 replication in tissue culture [80]. Viral replication was impacted due to HSV-1 gene expression being blocked in the nucleus but not in the cytoplasm in the presence of SPP inhibitors [80]. Importantly, (Z-LL)2-ketone administered to the eyes of mice infected with HSV-1 significantly decreased viral replication. Therefore, disruption of SPP activity may be a potential therapy for HSV-1 induced eye disease, and should be examined further, especially due to concern of acyclovir-resistant isolates and the lack of a prophylactic vaccine [81].
Cyclodextrin-based nanosponges as promising carriers for active agents
Published in Expert Opinion on Drug Delivery, 2019
Saeideh Allahyari, Francesco Trotta, Hadi Valizadeh, Mitra Jelvehgari, Parvin Zakeri-Milani
Acyclovir as a BCS class III drug [58] is a synthetic purine nucleoside analogous which is derived from guanine. This highly used antiviral agent is really effective against herpes simplex virus. There are some pharmacokinetic limitations in oral use of this lipophilic drug, like slow and incomplete absorption in GI tract. Because of its low oral bioavailability (ranges from 10% to 30%), increasing the administered dose will be necessary, however, increased toxicity and adverse reactions will be occurred too [57]. In one study for the aim of improving drug antiviral activity new drug delivery system was. In that study two different types of CDNSs, carboxylate (carb-) and non-carboxylated were used. Based on the study results, it was speculated that the acidic groups in carb-CDNSs interact electrostatically with amino groups in acyclovir and enhanced drug loading (about 30%) was observed. The in vitro release studies also showed more prolonged release kinetic in comparison with non-carb-CDNSs. The percentage of acyclovir release from carb-NSs and non-carb-NSs after 3 h were 22% and 70%, respectively, and no initial burst release was observed from those carriers. Cellular uptake of drug into Vero cells (African green monkey fibroblastoid kidney cells) was evaluated through fluorescent NSs which revealed high encapsulation of drug-carb-CDNS complex (about 200%) and drug-CDNS complex (about 70%) compared with plain drug [58].
Related Knowledge Centers
- Blister
- Prevalence
- Viral Shedding
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- Infection
- Skin
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- Alphaherpesvirus 2
- Viral Disease
- Sexually Transmitted Infection