Role of Human TRIM5? in Intrinsic Immunity.

ABSTRACT: Human immunodeficiency virus (HIV) has a very narrow host range. HIV type 1 (HIV-1) does not infect Old World monkeys, such as the rhesus monkey (Rh). Rh TRIM5? was identified as a factor that confers resistance, intrinsic immunity, to HIV-1 infection. Unfortunately, human TRIM5? is almost powerless to restrict HIV-1. However, human TRIM5? potently restricts N-tropic murine leukemia viruses (MLV) but not B-tropic MLV, indicating that human TRIM5? represents the restriction factor previously designated as Ref1. African green monkey TRIM5? represents another restriction factor previously designated as Lv1, which restricts both HIV-1 and simian immunodeficiency virus isolated from macaque (SIVmac) infection. TRIM5 is a member of the tripartite motif family containing RING, B-box2, and coiled-coil domains. The RING domain is frequently found in E3 ubiquitin ligase, and TRIM5? is thought to degrade viral core via ubiquitin-proteasome-dependent and -independent pathways. The alpha isoform of TRIM5 has an additional C-terminal PRYSPRY domain, which is a determinant of species-specific retrovirus restriction by TRIM5?. On the other hand, the target regions of viral capsid protein (CA) are scattered on the surface of core. A single amino acid difference in the surface-exposed loop between ?-helices 6 and 7 (L6/7) of HIV type 2 (HIV-2) CA affects viral sensitivity to human TRIM5? and was also shown to be associated with viral load in West African HIV-2 patients, indicating that human TRIM5? is a critical modulator of HIV-2 replication in vivo. Interestingly, L6/7 of CA corresponds to the MLV determinant of sensitivity to mouse factor Fv1, which potently restricts N-tropic MLV. In addition, human genetic polymorphisms also affect antiviral activity of human TRIM5?. Recently, human TRIM5? was shown to activate signaling pathways that lead to activation of NF-?B and AP-1 by interacting with TAK1 complex. TRIM5? is thus involved in control of viral infection in multiple ways.

SUBMITTER: Nakayama EE 

PROVIDER: S-EPMC3304089 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature