TY - JOUR
T1 - Ubiquitous human adeno-associated virus type 2 autonomously replicates in differentiating keratinocytes of a normal skin model
AU - Meyers, Craig
AU - Mane, Michael
AU - Kokorina, Natalia
AU - Alam, Samina
AU - Hermonat, Paul L.
N1 - Funding Information:
We thank Dr. Ken Berns for the titered AAV type 2 and adenovirus stocks used in this study. We also thank D. Huber, L. Budgeon, and R. Myers for excellent technical assistance. We thank Drs. David Spector, Wayne Gary, and Jason Chang for critical reading of the manuscript and the members of the C. Meyers and P. Hermonat laboratories for many helpful discussions. This work was supported by a grant consortium from the NIAID (AI42764 to P.L.H. and C.M.) and NCI (CA55051 to P.L.H.).
PY - 2000/7/5
Y1 - 2000/7/5
N2 - Since its discovery in 1966, adeno-associated virus type 2 (AAV) has been described as a helper-dependent parvovirus. However, in this study we demonstrate that AAV undergoes its complete life cycle, devoid of helper viruses or genotoxic agents, in the organotypic epithelial raft tissue culture system, a model of normal skin: AAV progeny production directly correlated with epithelial differentiation, as nondifferentiating keratinocytes were defective for this activity. Large nuclear virus arrays of particles of approximately 26 nm (parvovirus size) were observed in the granular layers of the raft epithelium by electron microscopy. Additionally, dosage-dependent histologic changes, some of which might be interpreted as cytopathology, were induced in the AAV-infected epithelial tissues. These data suggest a new biological model for AAV; that is, AAV is an epithelial- tropic autonomous parvovirus that can alter normal squamous differentiation. (C) 2000 Academic Press.
AB - Since its discovery in 1966, adeno-associated virus type 2 (AAV) has been described as a helper-dependent parvovirus. However, in this study we demonstrate that AAV undergoes its complete life cycle, devoid of helper viruses or genotoxic agents, in the organotypic epithelial raft tissue culture system, a model of normal skin: AAV progeny production directly correlated with epithelial differentiation, as nondifferentiating keratinocytes were defective for this activity. Large nuclear virus arrays of particles of approximately 26 nm (parvovirus size) were observed in the granular layers of the raft epithelium by electron microscopy. Additionally, dosage-dependent histologic changes, some of which might be interpreted as cytopathology, were induced in the AAV-infected epithelial tissues. These data suggest a new biological model for AAV; that is, AAV is an epithelial- tropic autonomous parvovirus that can alter normal squamous differentiation. (C) 2000 Academic Press.
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U2 - 10.1006/viro.2000.0385
DO - 10.1006/viro.2000.0385
M3 - Article
C2 - 10873777
AN - SCOPUS:0034608803
SN - 0042-6822
VL - 272
SP - 338
EP - 346
JO - Virology
JF - Virology
IS - 2
ER -