title: Infant lungs are preferentially infected by adenovirus and herpes simplex virus type 1 vectors: role of the tissue mesenchymal cells.
abstract: BACKGROUND
  Adenovirus (AD) and herpes-simplex-virus-1 (HSV-1) have been extensively applied as vectors for gene and cancer therapy in clinical trials. AD5, from which the vector was constructed, is a common respiratory virus that infects mainly infants, yet the reasons for infant sensitivity to infection, other than immunity, are not clear. HSV-1, usually a neurotropic virus, may also cause severe pneumonia or disseminated diseases in infants and immunocompromised patients.
  
  
  METHODS
  The tropism of these viruses to different human and mouse lung tissues of newborn and adult was studied in an ex vivo organ culture and it was also applied in vivo using a murine model.
  
  
  RESULTS
  The data obtained indicated preferential viral infection of young lung tissues versus adult tissues in organ culture. Further studies indicated that the preferential infection of young tissues was not related to differences in receptor expression or exposure but rather to the different distribution of cell types in these tissues. Murine and human young lungs consist of a relative abundance of mesenchymal cells and these cells were much more susceptible to viral infection compared to adjacent epithelial-pneumocyte cells. These observations were further confirmed using an in vivo model of mouse infection.
  
  
  CONCLUSIONS
  The similarity of the human and mouse tissues, with respect to viral vector tropism, validates the mouse model in studies of gene transfer to the lung. Furthermore, the results should facilitate the improved design of gene therapy trials for lung-related diseases in young and adults patients. Copyright © 2011 John Wiley & Sons, Ltd.
authors.affiliation: Department of Biochemistry, The Hebrew University, Hadassah Medical School Jerusalem, Israel.
authors.forename: Anda
authors.initials: A
authors.lastname: Massler
authors.forename: Dror
authors.initials: D
authors.lastname: Kolodkin-Gal
authors.forename: Karen
authors.initials: K
authors.lastname: Meir
authors.forename: Abed
authors.initials: A
authors.lastname: Khalaileh
authors.forename: Haya
authors.initials: H
authors.lastname: Falk
authors.forename: Uzi
authors.initials: U
authors.lastname: Izhar
authors.forename: Yoel
authors.initials: Y
authors.lastname: Shufaro
authors.forename: Amos
authors.initials: A
authors.lastname: Panet
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000328:Adult; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002522:Chlorocebus aethiops; D005333:Fetus / Q000166:cytology / Q000821:virology; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007223:Infant; D008168:Lung / Q000166:cytology* / Q000821:virology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014709:Vero Cells; D053586:Virus Internalization