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Species-specific, postentry barriers to primate immunodeficiency virus infection
W Hofmann1, D Schubert, J LaBonte
1Department of Cancer Immunology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of Virology
|November 13, 1999
Summary
This study investigated viral vector infection efficiency across mammalian species. Primate lentiviral vectors showed species-specific restrictions, suggesting broad cellular factors influence early infection.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Understanding lentiviral vector tropism is crucial for gene therapy and studying viral pathogenesis.
- Replication-defective viral vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV(mac)), and murine leukemia virus (MuLV) are valuable tools for studying viral entry and infection.
- Vesicular stomatitis virus (VSV) G glycoprotein pseudotyping enhances viral vector entry into diverse cell types.
Purpose of the Study:
- To examine the efficiency of postentry, early infection events using HIV-1, SIV(mac), and MuLV vectors pseudotyped with VSV G glycoprotein in target cells from various mammalian species.
- To identify species-specific barriers to lentiviral vector infection.
- To investigate the role of cellular factors in restricting early postentry events of primate immunodeficiency viruses.
Main Methods:
- Generation of replication-defective lentiviral vectors (HIV-1, SIV(mac), MuLV) pseudotyped with VSV G glycoprotein.
- Infection of various cell lines and primary cells from different mammalian species (Old World monkeys, New World monkeys, prosimians, rodents, rabbits, cows, pigs).
- Quantification of vector titers and assessment of vector expression levels in transduced cells.
Main Results:
- HIV-1 vectors showed significantly lower titers than SIV(mac) and MuLV vectors in Old World monkey cells.
- New World monkey cells exhibited much lower titers for the SIV(mac) vector compared to the HIV-1 vector.
- Prosimian cells were resistant to both HIV-1 and SIV(mac) vectors but susceptible to MuLV vectors. Rabbit cells were specifically resistant to the HIV-1 vector, with low expression in rodent, rabbit, cow, and pig cells.
- Early postentry restriction patterns largely coincided with species borders across diverse cell types.
Conclusions:
- Species-specific barriers significantly restrict early postentry events of primate immunodeficiency virus infection.
- These restrictions appear to involve widely expressed, species-specific cellular factors.
- The findings have implications for the development of lentiviral vectors for gene therapy and for understanding viral host range.