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A conserved mechanism of retrovirus restriction in mammals
1Wohl Virion Centre, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London W1P 6DB, United Kingdom.
Abstract:
The murine Fv1 gene restricts infection by N- or B-tropic murine leukemia viruses at a postentry, preintegration stage. The Fv1-sensitive viruses previously used for the study of Fv1 encode an ecotropic envelope gene and thus only infect rodent cells. Consequently, the study of Fv1 restriction has been carried out solely in mice and murine cell lines. By infection with retroviral vectors containing N- or B-tropic core and pantropic vesicular stomatitis virus-G envelope protein, we now demonstrate that cell lines derived from various mammalian species, including humans, have an Fv1-like retrovirus restriction function, preventing N-tropic vector infection. Like Fv1, restriction is directed at amino acid 110 of the viral capsid protein. In contrast to Fv1, the novel restriction is characterized by the absence of reverse-transcribed viral DNA. We speculate that these activities have been selected for by retroviral epidemics in the distant past.
Insights
Mammalian cells possess a novel retrovirus restriction function, similar to the murine Fv1 gene, that blocks N-tropic retroviral infections. This restriction targets viral capsid protein and prevents viral DNA formation.
Area of Science:
- Virology
- Genetics
- Molecular Biology
Background:
- The murine Fv1 gene restricts N- or B-tropic murine leukemia virus infection at a postentry, preintegration stage.
- Previous studies were limited to mice and murine cell lines due to ecotropic envelope genes of Fv1-sensitive viruses.
Purpose of the Study:
- To investigate if non-rodent mammalian cells possess Fv1-like retrovirus restriction functions.
- To characterize the mechanism and specificity of this novel restriction.
Main Methods:
- Infection of various mammalian cell lines with retroviral vectors encoding N- or B-tropic cores and a pantropic vesicular stomatitis virus-G envelope protein.
- Analysis of viral DNA and capsid protein interactions.
Main Results:
- Cell lines from various mammalian species, including humans, exhibit Fv1-like restriction against N-tropic retroviral vectors.
- Restriction targets amino acid 110 of the viral capsid protein.
- Unlike Fv1, this novel restriction is characterized by the absence of reverse-transcribed viral DNA.
Conclusions:
- A conserved retroviral restriction mechanism exists across mammalian species, potentially shaped by past retroviral epidemics.
- This discovery expands the understanding of host-pathogen interactions and viral restriction factors beyond murine models.