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At least 829 records · Page 46Linked to original sources
PubMed1996

Therapeutic potential of Cidofovir (HPMPC, Vistide) for the treatment of DNA virus (i.e. herpes-, papova-, pox- and adenovirus) infections.

(S)-1-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC, Cidofovir, Vistide) is an acyclic nucleoside phosphonate with broad-spectrum activity against a wide variety of DNA viruses including herpesviruses [Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV-6) and equine and bovine herpesviruses], papovaviruses [human polyoma virus and human papilloma virus (HPV)], adeno-, irido-, hepadna-, and poxviruses. HPMPC has proved effective against these viruses in different cell culture systems and/or animal models. The mechanism of action of HPMPC is based upon the interaction of its active intracellular metabolite, the diphosphorylated HPMPC derivative HPMPCpp, with the viral DNA polymerase. HPMPCpp has been shown to block CMV DNA synthesis by DNA chain termination following incorporation of two consecutive HPMPC molecules at the 3'-end of the DNA chain. HPMPC confers a prolonged antiviral action, which lasts for several days or weeks, thus allowing infrequent dosing (i.e. every week or every two weeks). This prolonged antiviral action is probably due to the very long intracellular half-life of the HPMPC metabolites, particularly the HPMPCp-choline adduct. In clinical studies, HPMPC has proved efficacious in the treatment of CMV retinitis, following both intravenous injection (3 or 5 mg/kg, every other week) and intravitreal injection (single dose of 20 micrograms per eye). Initial clinical trials also point to the efficacy of both systemic (intravenous) and topical HPMPC (1% ointment) in the treatment of acyclovir-resistant HSV infections, and of topical HPMPC (ointment or injection) in the treatment of pharyngeal, laryngeal and anogenital HPV infections. HPMPC is now being pursued in the topical and/or systemic (intravenous) treatment of various infections due to CMV, HSV, VZV, EBV, HPV, polyoma-, adeno- and poxviruses.

Animals↗
PubMed1985

In situ hybridization with biotinylated DNA probes: a rapid diagnostic test for adenovirus upper respiratory infections.

Adenovirus DNA was detected in cells from nasopharyngeal secretions of children with acute respiratory infections by in situ hybridization with biotinylated probes. The technique was easy to perform, giving rapid results which were well correlated with those of immunofluorescence assays of the same samples. Adenoviruses of subgroups B, C and E were detected equally well by probes prepared either from purified adenovirus type 5 or from a plasmid (A1) carrying a cloned insertion of BamH1 fragments C and D of adenovirus type 2 in pAT 153. The use of stable non-radioactive probes makes in situ hybridization a feasible assay for use in clinical laboratories with moderate resources.

Adenoviridae Infections↗
PubMed1988

Epithelium-specific response of cultured keratinocytes to infection with adenovirus type 2.

Adenoviruses are pathogenic for certain stratified squamous epithelia. The sites most frequently involved are the upper respiratory tract and oropharynx. Adenovirus infections of the epidermis are quite rare. We examined the virus-cell interactions of adenovirus type 2 (Ad2) and cultured human keratinocytes grown from a variety of body sites. Our intent was to explore the nature of the apparent epithelium-specific susceptibility to Ad2. In brief, we found that in vitro viral susceptibility of the keratinocytes could be reliably predicted based on whether the cells originated from an epidermal or oropharyngeal surface. Ad2 proceeded through a complete vegetative cycle when used to infect cultured keratinocytes from oropharyngeal sites (e.g., gingiva and soft palate). In contrast, Ad2 infection was severely restricted in keratinocytes from epidermal sites (e.g., foreskin, abdomen, and buttock). These results demonstrate that the in vitro response to infection with Ad2 reflects in vivo tissue-specific susceptibility. In vivo, cervical epithelium is rarely infected with Ad2 and yet in culture, cervical keratinocytes were fully permissive for Ad2 replication. We propose that the permissive or nonpermissive response to Ad2 may be regulated by a particular aspect of cell phenotype. Because the permissive responses seen in this study were all generated in keratinocytes from mucosal sites, it is possible the in vitro response to Ad2 reflects inherent differences between mucosal and epidermal keratinocytes.

Adenoviruses, Human↗
PubMed2003

Optimization of dendritic cell maturation and gene transfer by recombinant adenovirus.

Dendritic cells (DC) have vast potential for immunotherapy. Transferring therapeutic genes to DC may enhance their inherent T cell-stimulatory capacity. Recombinant adenovirus is the most efficient vehicle for DC gene transfer and can alone mature DC. We sought to define the parameters of adenovirus infection of murine bone marrow-derived DC (BMDC) and the concomitant impact on BMDC maturation. The efficiency of adenoviral gene transfer to DC depended on the mouse strain, the organ source of DC, and the level of DC maturation. C57BL/6 BMDC consistently had higher transgene expression than BALB/c DC. While BMDC had considerable GFP expression after AdGFP infection, adenovirus was relatively ineffective in accomplishing transgene expression in freshly isolated hepatic or splenic DC. BMDC that were relatively immature because of a shorter duration of culture had higher transgene expression after infection. Nevertheless, pretreatment of DC with exogenous stimulants such as LPS or TNF-alpha resulted in higher transgene expression. Maturation of BMDC depended only on virus entry but not viral gene or transgene expression. Therefore, DC maturation was disproportionately high compared to the percentage of DC that actually expressed the adenoviral transgene. Maturation by adenovirus was only seen in BMDC, but not in liver or splenic DC, and was more pronounced in DC from later in culture (day 12 versus day 6). There was a dose-response relationship, up to a threshold dose, between adenovirus infection and both DC maturation and enhancement of DC activation of antigen-specific T cells. Our findings underscore the importance of optimizing gene transfer to DC in designing strategies for immunotherapy.

Adenoviridae↗