Adenoviridae | EPFL Graph Search

Les Adenoviridae, ou adénovirus, sont une famille de virus qui regroupe une centaine de variétés, dont une quarantaine environ peut infecter l'humain. C'est en 1953 que ceux-ci ont été mis en évidence par à partir de fragments d'amygdale (qui lui donne son nom, du grec adến : glande, et non de « ADN »). Morphologie Les adénovirus sont des virus possédant de l'ADN double brin linéaire (, pb), les deux brins d'ADN possèdent à leurs extrémités des séquences répétées inversées qui permettent aux molécules monocaténaires (simple brin) de se circulariser (la protéine p55 permet la circularisation). Les adénovirus sont des particules d'un diamètre de , sans enveloppe, à capside icosaédrique formée de 252 capsomères (240 et 12 pentons). Les capsomères situés aux sommets de l'icosaèdre sont des pentons prolongés par une fibre de longueur variable et terminée par l'antigène Y, responsable de la propriété d'hémagglutination. Protéines de la capside L’hexon est constitu

Solar disinfection of viruses (SODIS): inactivation of coliphages MS2 and phiX174, human adenovirus and echovirus in water from Switzerland and India

Alex Dionisio Calado

Access to safe drinking water remains a challenge in many regions of the world. New methods to treat drinking water are constantly developped and improved in both in industrialised countries and in developing countries. SODIS is an interesting household-level disinfection technique that simply consists of pouring water into a PET bottle and exposing it to sunlight for at least 6 hours. Bacteria are efficiently inactivated by sunlight during SODIS, but the efficiency of SODIS on virus removal is much less studied. In this work, the inactivation of bacteriophages MS2 and phiX174, and human echovirus and adenovirus was studied in three different waters, two from India and one from Switzerland. Good removal (4 logs in 6 hours at 22°C and a fluence rate of 600 1.34 kJ/cm2) of MS2 was achieved in Swiss tap water, while less efficient inactivation was achieved in both Indian waters for MS2 and echovirus (1 log in 6 hours at 22°C and a fluence rate of 1.34 kJ/cm2). Both phiX174 and adenovirus were much more resistant to SODIS disinfection and less than 1 log of inactivation was obtained in Swiss tap water for phiX174. However, inactivation was not significantly different from the dark control in Indian water and for all experiments with adenovirus. Echovirus was inactivated similarly than MS2 and adenovirus was equally slow as phiX174. An increased temperature during SODIS enhanced inactivation substantially; 6 logs in 6 hours could be expected at 45 °C and with a fluence rate of 1.34 kJ/cm2. Indirect-solar inactivation was responsible for the MS2 removal, while direct inactivation via sunlight absorption of genome was not occurring during SODIS. We argue that iron could be responsible for the formation of reactive oxygen species which react with the viruses and yield their inactivation. The slower inactivation in Indian waters was probably due to the quenching effect of the higher concentration of organic matter. Removal of echoviruses during SODIS could be sufficient (4 logs in 6 hours) particularly at higher temperatures and for water with a low organic matter content. In contrast, SODIS may not be effective to remove Adenoviruses.

2013

On the replication of adeno-associated virus in the presence or absence of viral helper functions

Anika Ekrut

Adeno-associated virus (AAV) is a small non-enveloped virus and as a member of the parvovirus family, it contains a single stranded DNA genome. AAV's life cycle in vitro is strongly dependent not only on cellular factors but also on helper functions provided by other viruses, for example adenovirus, herpes virus and, to a certain extent, papillomavirus (HPV). Although AAVs are wide spread throughout the human population, no disease is yet associated with them. Accordingly, AAV became attractive as a vector for gene therapy studies, but even though the virus is well studied in vitro and now used in clinical trials as a vector, not much is known about AAV infection in vivo. AAV was initially isolated from humans together with its helper adenovirus. However, adenovirus-independent replication of AAV has been reported for a number of cellular situations, including differentiating keratinocytes with or without the presence of HPV, and in cells with an activated DNA damage response due to genotoxic agents. In the work reported here we have undertaken a systematic study of these alternative helper activities with a view to evaluating their contribution to natural infections by AAV. We used three different systems of cultured keratinocytes and showed that in each case in vitro differentiation was achieved. In two of these, the cells were from HPV-induced lesions. We found that AAV replicates efficiently in differentiating monolayer foreskin keratinocytes in the presence but not in the absence of adenovirus. Likewise naturally HPV-infected cervical keratinocytes only support the full life cycle of AAV if adenovirus is present. Even though HPV can provide certain helper functions, it is less efficient as a helper than adenovirus. We also exploited osteosarcoma cells, which are particularly well infected by AAV. Our results indicate that U2OS osteosarcoma cells are semi-permissive for AAV growth. Induction of a DNA damage response in these cells, or in HPV-containing keratinocytes, stimulates AAV genome amplification. Although AAV replication in the absence of helper virus can readily be demonstrated, this is either at a relatively low level or limited to part of the AAV growth cycle. We conclude that although these alternative helper systems can contribute to the natural history of AAV, the presence of an efficient helper virus seems likely to be needed for AAV to persist in the human population.

EPFL2009

Patchy Amphiphilic Dendrimers Bind Adenovirus and Control Its Host Interactions and in Vivo Distribution

Weina Liu, Francesco Stellacci

The surface of proteins is heterogeneous with sophisticated but precise hydrophobic and hydrophilic patches, which is essential for their diverse biological functions. To emulate such distinct surface patterns on macromolecules, we used rigid spherical synthetic dendrimers (polyphenylene dendrimers) to provide controlled amphiphilic surface patches with molecular precision. We identified an,. I optimal spatial arrangement of these patches on certain dendrimers that enabled their interaction with human adenovirus 5 (Ads). Patchy dendrimers bound to the surface of Ads formed a synthetic polymer corona that greatly altered various host interactions of Ads as well as in vivo distribution. The dendrimer corona (1) improved the ability of Ad5-derived gene transfer vectors to transduce cells deficient for the primary Ad5 cell membrane receptor and (2) modulated the binding of Ads to blood coagulation factor X, one of the most critical virus host interactions in the bloodstream. It significantly enhanced the transduction efficiency of Ad5 while also protecting it from neutralization by natural antibodies and the complement system in human whole blood. Ads with a synthetic dendrimer corona revealed profoundly altered in vivo distribution, improved transduction of heart, and dampened vector sequestration by liver and spleen. We propose the design of bioactive polymers that bind protein surfaces solely based on their amphiphilic surface patches and protect against a naturally occurring protein corona, which is highly attractive to improve Ad5-based in vivo gene therapy applications.