Viruses herpesvirus

Herpesviruses range in size from 120 to 300 nm and have DNA genomes and outer lipid membranes (envelopes). As enveloped viruses, herpesviruses are sensitive to drying and adverse conditions. Herpesviruses are spread by inoculation of susceptible mucous membranes or direct cell-to-cell contact. Over 100 herpesviruses have been identified, but only 5 cause human eye infections with any frequency herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus. Herpesviruses can cause blepharitis, conjunctivitis, epithelial and stromal keratitis, uveitis, retinitis, and ARN. HSV-1 is the most frequent cause of primary and recurrent eye disease. The host immime system influences the rates of reactivation. Immimocompromised patients tend to have more frequent reactivations and more severe disease manifestations. The strain of virus also affects the... 

Apoptosis of an infected cell can either be caused by a signal from outside the cell, e.g., a virus-specific cytotoxic T cell, or caused by a signal from inside the cell and may occur cell autonomously in the absence of an immune response toward the virus. Herpesviruses have evolved a number of strategies to interfere with both cell-autonomous and CTL-induced apoptosis. 

However, acyclic nucleotide analogs (acyclic nucleoside phosphonates) have been developed, which carry one phosphonate moiety and require only the two subsequent phosphorylation steps (De Clercq et al. 1978). Independent of virus-encoded kinases, they display a broader spectrum of efficacy. This class comprises important drugs against HIV (tenofovir) and HBV (adefovir, tenofovir), as well as cidofovir, which is approved for use against CMV retinitis, but also displays an exceptionally broad efficacy profile against many herpesviruses, adenovirus, poxviruses, and papillomaviruses (De Clercq and Holy 2005). 

Cidofovir (Fig. 2) has been formally approved for the treatment of CMV retinitis in AIDS patients, where it is administered intravenously at a dose not exceeding 5 mg/kg once weekly during the first two weeks (and every other week thereafter). Cidofovir is also used off label for the treatment of human papilloma virus (HPV) infections (i.e., cutaneous warts, anogenital warts, laryngeal and pharyngeal papilloma), polyomavirus [i.e., progressive (i.e., multifocal leukoencephalopathy (PML)], adenovirus, herpesvirus, and poxvirus (i.e., molluscum contagiosum) infections, where it can be administered intravenously (at a dose of < 5 mg/kg once weekly or every other week) or topically as a 1% gel or cream (De Clercq and Holy 2005). Especially in immunosuppressed patients (i.e., transplant recipients), local treatment of HPV-associated lesions has often yielded spectacular results (Bonatti etal.2007). 

Since the pioneering work of Kleymann et al. (2002), Betz et al. (2002), Baumeister et al. (2007), and Crute et al. (2002), who showed that compounds identified as inhibitors of the helicase-primase enzyme complex could alleviate herpesvirus-induced disease in animal models, the attention of researchers developing antiviral compounds has been drawn more and more towards the virus-encoded helicases, particularly those of Herpes viruses and of RNA viruses such as Hepatitis C Virus (HCV) and SAKS coronavirus (SARS-CoV). Enzyme activity is usually assayed by measuring NTPase activity in the presence of an appropriate nucleic acid co-substrate although, more recently, novel fiuorimetric and luminescence principles have been applied to the measurement of strand unwinding and/or translocation of the protein along the nucleic acid (Frick 2003, 2006). 

Apart from offering a new and highly specific approach to the inhibition of herpesviruses, this new mechanism of action could potentially also have beneficial immunological consequences. During treatment with BAY 38-4766, viral protein synthesis continues, but due to the lack of monomeric genomic length DNA, only empty particles (dense bodies) can be formed. It is conceivable that these non-infections viral particles could aid the establishment of an antiviral immune response, leading to better control of the virus by the host. This mechanism appears... 

Furlini G, Vignoli M, Ramazzotti E, Re MC, Visani G, La P (1996) A concurrent human herpesvirus-6 infection renders two human hematopoietic progenitor (TF-1 and KG-1) ceU lines susceptible to human immunodeficiency virus type-1. Blood 87(ll) 4737-4745... 

Rucker J, Edinger AL, Sharron M et al (1997) Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodefidency viruses. J Virol 71 8999-9007... 

Over 20 infectious agents have been incriminated as etiologic agents for many the causal relationship has been disproved, and for others there is conflicting evidence. Human herpesvirus 6 (HHV-6) is currently the most likely causative virus. HHV-6 may initiate the autoimmune processes of MS in one of two ways. First, HHV-6 is structurally similar to myelin basic protein. When T cells become sensitive to HHV-6, the cells may attack myelin basic protein. Second, HHV-6 may directly stimulate the complement cascade, activating autoimmune processes.5 Infection with HHV-6 alone cannot fully explain MS, because HHV-6 is found in 75% of all people, but MS is much more rare. 

A dubious, but not uninteresting case can be made for mammalian herpesviruses, large double-stranded DNA viruses, which might have evolved from their mammalian hosts. Their nonstructural (enzymatic and control) viral proteins are similar to those of nonviral host proteins (McGeoch and Davidson, 1995), although recombination might also explain these similarities. 

When administered as valaciclovir, aciclovir is released during absorption, and 60% of the drug reaches the bloodstream, as described above. Site activation also occurs in herpesvirus-infected cells where aciclovir is biochemically transformed to the phosphorylated active drug by virus-specific thymidine kinase [74]. 

In spite of this, only social reorganization stress reactivated the latent virus. This study further supports the hypothesis that psychological stress is capable of reactivating latent herpesviruses, and shows that not all stressors produce the same health outcomes, implying that there are differences in physiological pathways associated with different types of stressors. 

IARC, Epstein-Barr virus and Kaposi s sarcoma herpesvirus/human herpes virus 8IARC Press, Lyon, France, 1997. 

Herpes simplex vaccine, 25 498-499 Herpes simplex viruses, 3 136 Herpesviruses, 3 136 Herpes zoster vaccine, 25 496-497 Herschel-Bulkley model, 21 705 Herschel effect, 19 204 Herz compounds, 23 643... 

Feuh, K., et ah. Immune evasion by a novel family of viral PHD/LAP-finger proteins of gamma-2 herpesviruses and poxviruses. Virus Res, 2002, 88(1-2), 55-69. 

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