Abstract:
:Vectors derived from lentiviruses provide a promising gene delivery system. We examined the in vivo gene transfer efficiency and tissue or cell tropism of a feline immunodeficiency virus (FIV)-based lentiviral vector pseudotyped with the glycoproteins from Ross River Virus (RRV). RRV glycoproteins were efficiently incorporated into FIV virions, generating preparations of FIV vector, which after concentration attain titers up to 1.5 x 10(8) TU/ml. After systemic administration, RRV-pseudotyped FIV vectors (RRV/FIV) predominantly transduced the liver of recipient mice. Transduction efficiency in the liver with the RRV/FIV was ca. 20-fold higher than that achieved with the vesicular stomatitis virus G protein (VSV-G) pseudotype. Moreover, in comparison to VSV-G, the RRV glycoproteins caused less cytotoxicity, as determined from the levels of glutamic pyruvic transaminase and glutamic oxalacetic transaminase in serum. Although hepatocytes were the main liver cell type transduced, nonhepatocytes (mainly Kupffer cells) were also transduced. The percentages of the transduced nonhepatocytes were comparable between RRV and VSV-G pseudotypes and did not correlate with the production of antibody against the transgene product. After injection into brain, RRV/FIV preferentially transduced neuroglial cells (astrocytes and oligodendrocytes). In contrast to the VSV-G protein that targets predominantly neurons, <10% of the brain cells transduced with the RRV pseudotyped vector were neurons. Finally, the gene transfer efficiencies of RRV/FIV after direct application to skeletal muscle or airway were also examined and, although transgene-expressing cells were detected, their proportions were low. Our data support the utility of RRV glycoprotein-pseudotyped FIV lentiviral vectors for hepatocyte- and neuroglia-related disease applications.
journal_name
J Viroljournal_title
Journal of virologyauthors
Kang Y,Stein CS,Heth JA,Sinn PL,Penisten AK,Staber PD,Ratliff KL,Shen H,Barker CK,Martins I,Sharkey CM,Sanders DA,McCray PB Jr,Davidson BLdoi
10.1128/jvi.76.18.9378-9388.2002subject
Has Abstractpub_date
2002-09-01 00:00:00pages
9378-88issue
18eissn
0022-538Xissn
1098-5514journal_volume
76pub_type
杂志文章abstract::West Nile virus (WNV) replicates in the skin; however, cell targets in the skin have not been identified. In the current studies, WNV infected the epidermis and adnexal glands of mouse skin, and the epidermal cells were identified as keratinocytes by double labeling for WNV antigen and keratin 10. Inoculation of mice ...
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.4.812-819.1975
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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