News & Updates
Search Research Content
Resource Finder at Kennedy Krieger Institute
A free resource that provides access to information and support for individuals and families living with developmental disabilities.
Virus-specific effects of TRIM5α(rh) RING domain functions on restriction of retroviruses.
|Title||Virus-specific effects of TRIM5α(rh) RING domain functions on restriction of retroviruses.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Li X, Kim J, Song B, Finzi A, Pacheco B, Sodroski J|
|Journal||Journal of virology|
|Date Published||2013 Jul|
The tripartite motif protein TRIM5α restricts particular retrovirus infections by binding to the incoming capsid and inhibiting the early stage of virus infection. The TRIM5α RING domain exhibits E3 ubiquitin ligase activity and assists the higher-order association of TRIM5α dimers, which promotes capsid binding. We characterized a panel of RING domain mutants of the rhesus monkey TRIM5α (TRIM5α(rh)) protein. The RING domain function that significantly contributed to retroviral restriction depended upon the restricted virus. The E3 ubiquitin ligase activity of the RING domain contributes to the potency of HIV-1 restriction. Nonetheless, TRIM5α(rh) mutants without detectable E3 ubiquitin ligase activity still blocked reverse transcription and inhibited HIV-1 infection at a moderate level. When TRIM5α(rh) capsid binding was weakened by substitution with a less efficient B30.2/SPRY domain, the promotion of higher-order association by the RING domain was more important to HIV-1 restriction than its E3 ubiquitin ligase activity. For the restriction of N-tropic murine leukemia virus (N-MLV) and equine infectious anemia virus (EIAV) infection, promotion of higher-order association represented the major contribution of the RING domain. Thus, both identity of the target virus and the B30.2/SPRY domain-mediated affinity for the viral capsid determine the relative contribution of the two known RING domain functions to TRIM5α restriction of retrovirus infection.
|Alternate Journal||J. Virol.|