Viral replication, herpes simplex

Other types of replication-deficient viral vectors that have been used in the gene therapy field include Herpes simplex viral (HSV) vectors that (1) are able to transduce nondividing cells and (2) are highly infective for neurologic tissue and vaccinia vectors. Vaccinia vectors in turn (1) are able to transduce nondividing cells and (2) have the ability to efficiently infect many types of cells. The primary safety concerns for HSV vectors are the potential for tropism to the CNS and the potential for latency and reactivation. Vaccinia vectors contain the same backbone as the smallpox vaccine, thus the available safety databases for vaccinia administration in humans consist primarily of preventive vaccination in a healthy population. Principal safety concerns with the use of vaccinia vectors include (1) their ability to replicate in humans and possibly... 

Type I (IFN-a/P) and type II (IFN-y) IFNs are major lines of defense against viral infection. IFNs mediate direct antiviral effector mechanisms that inhibit multiple steps of viral replication (Samuel 1991 Vilcek and Sen 1996). For example, 2, 5 -oligoadenylate synthetase (2, 5 -OAS) activates ribonuclease L, which degrades mRNA and limits the accumulation of viral transcripts. Protein kinase R blocks translation of viral transcripts by phosphorylating translation initiation factor eIF-2. Mx proteins block influenza, vesicular stomatitis virus, and herpes simplex virus replication by an unknown mechanism. 

Most recently (36) another drug [9-(2-hydroxyethoxymethyl)guanine] has been described which inhibits herpes simplex virus replication without affecting any virus infected cells. The basis of selectivity appears to depend upon the ability of the drug to be phosphorylated (by a virus-coded thymidine kinase) to compounds which are toxic to the viral genetic material. 

Saxton, R. E., and Stevens, J. C., 1972, Restriction of herpes simplex virus replication by poliovirus A selective inhibition of viral translation, Virology 48 207. 

Acyclovir (Zovirax) and penciclovir (Denavir) are the only topical antiviral dragp currently available These dragp inhibit viral replication. Acyclovir is used in the treatment of initial episodes of genital herpes, as well as heqies simplex virus infections in immunocompromised patients (patients with an immune system incapable of fighting infection). Penciclovir is used for the treatment of recurrent herpes labialis (cold sores) in adults. 

Despite the protective effect of NO against various viral infections, workers in several studies have shown a harmful role of NO in many systems. NO seems to play a part in the development of pneumonia caused by influenza virus [128], in the pathogenesis in mice of tick-borne encephalitis flavivirus infection [131], and in worsening the course of the murine myocarditis caused by coxsackievirus B3 [132]. In addition, pneumonia in mice induced by herpes simplex virus type 1 could be suppressed by the inhibitor of iNOS [133]. The issue of whether NO acts as an inhibitor of viral replication or as a harmful agent, therefore, remains unanswered. This issue is particularly evident in HIV-1 infection, since NO seems to act as a double-edged sword in the pathogenesis of HIV-1. 

Viral replication as exemplified by Herpes simplex viruses (A) (1) The... 

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Aciclovir is phosphorylated preferentially by herpes simplex virus-coded thymidine kinase and following further phosphorylation aciclovir triphosphate interferes with herpes virus DNA polymerase and viral DNA replication. Aciclovir topical cream is indicated in the management of initial genital herpes and in limited non-life threatening mucocutaneous herpes simplex virus infections in immunocompromised patients. 

Mechanism of Action A synthetic nucleoside that inhibits viral DNA synthesis. Therapeutic Effect Suppresses replication of herpes simplex virus and varicella-zoster virus. 

Mechanism of Action Penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Therapeutic Effect An antiviral compound that has inhibitory activity against herpes simplex virus types 1 (HSV-1)... 

Mechanism of Action Avirustatic antiviral that is converted to acyclovir triphosphate, becoming part of the viral DNA chain. Therapeutic Effect Interferes with DNA synthesis and replication of herpes simplex virus and varicella-zoster virus. Pharmacokinetics Rapidly absorbed after PO administration. Protein binding 13%-18%. Rapidly converted by hydrolysis to the active compound acyclovir. Widely distributed to tissues and body fluids (including cerebrospinal fluid CSF ). Primarily eliminated in urine. Removed by hemodialysis. Half-life 2.5-3.3 hr (increased in impaired renal function). 

Other notable research by Elion led to the development of the antiviral drug Acyclovir (acycloguanosine), which has been used to treat the herpes simplex viruses. Her studies during the 1970s showed that Acyclovir inhibited viral replication by interfering with viral DNA synthesis. The sub-... 

Stow ND, McMonagle E (1982) Propagation of foreign DNA sequences linked to a herpes simplex virus origin of replication. In Eucaryotic Viral Vectors (Gluzman Y, ed), pp 199—204. Cold Spring Har bor Cold Spring Harbor Laboratory. 

Ocular antiviral chemotherapy in the horse is adapted from that used in herpes simplex virus (HSV) and varicella zoster keratitis in humans. The agents used are nucleotide analogs capable of inhibiting viral replication by competitive inhibition of the uptake of the nucleotide into the viral genome. These agents are virustatic and require an intact immune system to suppress or eliminate the virus from the eye. They probably do not eradicate any latent infection. The antiviral drugs available currently do not penetrate intact comeal epithelium and are poorly disseminated within the comeal stroma. The availability of these dmgs will vary in different countries and some may only be obtained from hospital pharmacies. 

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