The design of artificial retroviral restriction factors
- Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom)
- Division Molecular Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom)
In addition to the ability to bind the retroviral capsid protein, the retroviral restriction factors Fv1, Trim5{alpha} and Trim5-CypA share the common property of containing sequences that promote self-association. Otherwise Fv1 and Trim5{alpha} appear unrelated. Mutational analyses showed that restriction was invariably lost when changes designed to disrupt the sequences responsible for multimerization were introduced. A novel restriction protein could be obtained by substituting sequences from the self-associating domain of Fv1 for the Trim5 sequences in Trim5-CypA. Similarly, a fusion protein containing cyclophilin A joined to arfaptin2, a protein known to form extended dimers, was also shown to restrict HIV-1. Hence, multimerization of a capsid-binding domain could be the common minimum design feature for capsid-dependent retroviral restriction factors. However, not all domains that promote multimerization can substitute for the N-terminal domains of Fv1 and Trim5{alpha}. Moreover, only CypA can provide a capsid-binding site with different N-terminal domains. It is suggested that the spatial relationship between the multiple target binding sites may be important for restriction.
- OSTI ID:
- 21077963
- Journal Information:
- Virology, Vol. 365, Issue 2; Other Information: DOI: 10.1016/j.virol.2007.04.005; PII: S0042-6822(07)00254-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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