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 TRIM5α was identified as a factor that confers resistance, intrinsic immunity, to HIV-1 infection. Unfortunately, human TRIM5α is almost powerless to restrict HIV-1. However, human TRIM5α potently restricts N-tropic murine leukemia viruses (MLV) but not B-tropic MLV, indicating that human TRIM5α represents the restriction factor previously designated as Ref1. African green monkey TRIM5α 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 TRIM5α 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 TRIM5α. 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 α-helices 6 and 7 (L6/7) of HIV type 2 (HIV-2) CA affects viral sensitivity to human TRIM5α and was also shown to be associated with viral load in West African HIV-2 patients, indicating that human TRIM5α 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 TRIM5α. Recently, human TRIM5α was shown to activate signaling pathways that lead to activation of NF-κB and AP-1 by interacting with TAK1 complex. TRIM5α is thus involved in control of viral infection in multiple ways.
Highlights
The acquired immune response, both humoral and cellular immunity, requires lymphocyte differentiation and education for effective protection of the host from invasive infection
African green monkey TRIM5α represents another restriction factor previously designated as Lv1, which restricts both Human immunodeficiency virus (HIV)-1 and simian immunodeficiency virus isolated from macaque (SIVmac) infection
We found that 17 amino acid residues and the adjacent 20-amino acid duplication www.frontiersin.org in the variable region 1 (V1) of African green monkey (AGM) TRIM5α determined species-specific restriction against SIVmac (Nakayama et al, 2005)
Summary
The acquired immune response, both humoral and cellular immunity, requires lymphocyte differentiation and education for effective protection of the host from invasive infection. Most toll-like receptors (TLRs), which play a critical role in pattern recognition of invaders, such as double-stranded RNA, lipopolysaccharide (LPS), and CpG DNA, are expressed on macrophages and dendritic cells Aside from these conventional immunological definitions, many pieces of evidence provide a new concept of potent protection from viral infection designated as intrinsic immunity. It is constitutively expressed and active in many cells, and does not require any virus-triggered signaling or intercellular communication. Susceptibility of mouse cells to murine leukemia virus (MLV) infection is determined by a restriction factor called Fv1 (Lilly, 1970; Pincus et al, 1971, 1975). The Fv1b allele present in BALB/c mice blocks infection by so-called N-tropic MLV (N-MLV).
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