Adenovirus infections

Although ribavirin monotherapy is ineffective against HCV, oral ribavirin in combination with inter-feron-a (Rebatron) is approved for this indication and is effective in patients resistant to interferon therapy alone. Intravenous ribavirin may be useful in the therapy of Hantaan virus infection, Crimean or Congo virus hemorrhagic fever, Lassa fever, and severe adenovirus infection. 

Adenovirus Infects nonproliferating cells, nonintegrating Immunogenic, small DNA capacity (7.5 kb), replication risk, repeated injections required for long-term expression... 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

C. R. Miller, D. J. Buchsbaum, P. N. Reynolds, J. T. Douglas, G. Y. Gillespie, M. S. Mayo, D. Raben, and D. T. Curiel, Differential susceptibility of primary and established human glioma cells to adenovirus infection targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer, Cancer Res. 58 5138 (1998). 

M. Chillon, A. Bosch, J. Zabner, L. Law, D. Armentano, M. J. Welsh, and B. L. Davidson, Group D adenoviruses infect primary central nervous system cells more efficiently than those from group C, J. Virol. 73 2537 (1999). 

The routes of delivery of rAAV in animal models have been largely based upon the specific needs dictated by the disease process to be treated. For example, rAAV-cystic fibrosis transmembrane conductance regulator (CFTR) vectors that have been developed for treatment of cystic fibrosis (CF) were tested in New Zealand white rabbits and in rhesus macaques by the endobronchial route (Flotte et al., 1993 Afione et al., 1996 Conrad et al., 1996). In each instance aliquots of vector were instilled directly into the lumen of a bronchus through a fiberoptic bronchoscope. Vector DNA transfer and mRNA expression were detectable (albeit at low levels) for more than 6 months in each instance, without any indication of inflammation or any other toxicity. Studies in rhesus monkeys also indicated that the likelihood of rescue of rAAV by concomitant wild-type AAV and adenovirus infection was low. These studies... 

Adenovirus Infection of non-dividing cells Attaining high titre in culture Highly immunogenic Short-term expression... 

Relatively innocuous factors can also sometimes influence liver enzyme activity. For example, the metabolic elimination of the bronchodilator theophylline has been reported to be prolonged in patients with influenza A or adenovirus infections. In 1990, an influenza epidemic in Seattle resulted in the admission of 11 children with high serum levels of theophylline and confirmed drug toxicity. These effects appear to be confined to cytochrome P450-based drug biotransformation. They may be related to the generation of interferons as a result of these infections, which, presumably, are causally related to the inhibitory effect on hydroxylases and demethylases. 

This section contains information primarily about the antiviral activity, pharmacology, and treatment of herpesvirus infections. There is limited information on the antiviral treatment of adenovirus infections. The antiretroviral agents used to treat RNA viruses responsible fc>r AIDS are listed and their functions reviewed. However, there is no information on clinical trials pertaining to antiretroviral agents. 

A number of studies have indicated that CAR is the m or host cell determinant of adenovirus infection in vivo. CAR has been shown to be highly expressed in the heart (Tomko et at, 1997), and this observation is consistent with adenovirus-mediated gene delivery to cardiac tissue in vivo (Rosengart et at, 1999). GAR expression has been reported to be low or absent on primary human fibroblasts (Hidaka et al., 1999) and most peripheral blood cells (Leon et al., 1998 Huang et al., 1997), and these cell types have proved difficult to transduce with adenovirus vectors. In more recent studies, peripheral blood lymphocytes derived from transgenic mice expressing human GAR were shown to permit efficient adenovirus-mediated gene delivery (Schmidt et al, 2000). 

Thome TE, Voelkel-Johnson C, Casey WM, Parks LW, Faster SM. The activity of cytosolic phospholipase A2 is required for the lysis of adenovirus-infected cells by tumor necrosis factor. J. 

Adenoviruses can be the cause of hepatitis in newborns or immunosuppressed persons, sometimes even with a fulminant course. They bring about the formation of inclusion bodies in the hepatocellular nuclei. Adenovirus infections can be diagnosed either serologically or by virus isolation. (77-79)... 

Hartman ZC, Kiang A, Everett RS et al. Adenovirus infection triggers a rapid, MyD88-rcgulated transcriptome response critical to acute-phase and adaptive immune responses in vivo. J Virol 2007 81(4) 1796-1812. 

Cavalli-Bjorkman N, Osby E, Lundin J, Kalin M, Osterborg A, Gruber A. Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B cell chronic lymphocytic leukemia. Med Oncol 2002 19(4) 277-80. 

Figure 2 The Sertoli cell extends from the base of the seminiferous tubule (bottom right) to the lumen (upper left) and has numerous cytoplasmic projections that surround and support germ cells. In this maximum intensity projection of 13 series confocal images, a single Sertoli cell in an intact seminiferous tubule is visible because of green fluorescent protein expression following adenovirus infection. The Sertoli cell nucleus is visible in the basal cytoplasm surrounded by brightfluorescence. The overall length ofthis Sertoli is approximately 100 /xm.

Zabner J, Freimuth P, Puga A, Fabrega A, Welsh MJ. 1997. Lack of high affinity fiber receptor activity explains the resistance of ciliated airway epithelia to adenovirus infection. J. Clin. Invest. 100 1144 19... 

Adenovirus has been increasingly recognized as a cause of morbidity and mortality among immunocompromised patients owing to transplant and congenital immunodeficiency.Rarely adenovirus infection has been described in HIV-infected patients. " Characteristic... 

Yi ES, Powell HC. Adenovirus infection of the duodenum in an AIDS patient an ultrastructural study. Ultrastruct Pathol. 1994 18 549-551. 

DiPolo A, Aigner J, Dunn RJ, Bray GM, Aguayo AJ. Prolonged delivery of brain-derived neurotropohic factor by adenovirus-infected Muller cells temporarily rescues injured retinal ganglion cells. Proc Natl Acad Sci USA 1998 95 3978-3983. 

Fig, 6.4 Mean cell size of adenovirus-infected cells resulting from different processing methodologies. Particle size was measured using the Coulter Multisizer II to determine cell sizes within the... 

Fig. 6.7 TMAE analytical HPLC chromatogram, showing 260 nm absorbance traces of an non-in-fected cell harvest control (A) and adenovirus infected cell harvest sample (B). Chromatograms were generated using a HP 1100 system with a Fractogel EMD Tentacle Ion-Exchanger resin in a...

I FIQURE 14.23 Transcriptional tatgeting in virotherapy. A tumor-specific promoter is engineered into the adenovirus. The adenovirus infects many cells, but it is activated to replicate only in the cancer cell. ( > 2003 Terese Viinslow.)... 

Manufacture Scale-Up. The adenovirus harvest process consisted of three general steps concentration, lysis, and clarification. In the small-scale process, the intact adenovirus-infected cells in culture medium were aliquoted and batch centrifuged to achieve a 30-fold concentration, and the supernatant was manually removed and replaced with a smaller volume of the freeze buffer. Although sufficing for harvest volumes of no more than lOL, such a manual process would prove to be inadequate on a larger manufacturing scale. 

Association of adenovirus infection with human obesity. Obes. Res. 5, 464-469. 

The exacerbation of asthmatic responses is most frequently caused by a pulmonary viral infection, such as influenza, rhino, or adenovirus infections (81-89). Recent data has indicated that rhinoviral infections are the most common cause of severe asthma exacerbations. In addition to exacerbating asthmatic responses, severe respiratory syncytial virus (RSV) infections early in childhood appears... 

Bruder JT, Jie T, McVey DL, Kovesdi I (1997) Expression of gpl9K increases the persistence of transgene expression from an adenovirus vector in the mouse lung and liver. J Virol 71 7623-7628 Bruder JT, Kovesdi I (1997) Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression. J Virol 71 398-404 Burgert H-G (1996) Subversion of the MHC class I antigen presentation pathway by adenoviruses and herpes simplex viruses. Trends Microbiol 4 107-112... 

---