The human T-cell leukemia virus type 1 p13II protein: effects on mitochondrial function and cell growth

Abstract

Abstractp13 II of human T-cell leukemia virus type 1 (HTLV-1) is an 87-amino-acid protein that is targeted to the inner mitochondrial membrane. p13 II alters mitochondrial membrane permeability, producing a rapid, membrane potential-dependent influx of K þ . These changes result in increased mitochondrial matrix volume and fragmentation and may lead to depolarization and alterations in mitochondrial Ca 2 þ uptake/retention capacity. At the cellular level, p13 II has been found to interfere with cell proliferation and transformation and to promote apoptosis induced by ceramide and Fas ligand. Assays carried out in T cells (the major targets of HTLV-1 infection in vivo) demonstrate that p13 II -mediated sensitization to Fas ligand-induced apoptosis can be blocked by an inhibitor of Ras farnesylation, thus implicating Ras signaling as a downstream target of p13 II function. Cell Death and Differentiation (2005) 12, 905-915.

Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles

“…p13 contains a mitochondrial targeting signal spanning amino acids 21-30 25,26 and localizes to mitochondria when expressed Culture supernatants were harvested 48 and 72 hours after transfection and extracellular p19 Gag levels measured by ELISA assay. Western blot analysis for intracellular p24 Gag, Tax, and actin was performed on whole-cell lysates from 72-hour cultures.…”

“…It accumulates in the inner membrane of the mitochondria and modulates K ϩ permeability and reactive oxygen species, thereby altering the morphology and function of mitochondria. [25][26][27] Evidence of p13 expression in HTLV-1-infected cells is indirect, because only the presence of mRNA has been demonstrated in both in vitro and ex vivo studies. [28][29][30] orf -II appears to be dispensable for viral infection and transformation of T cells in vitro; however, its requirement in HTLV-1 infection of rabbits remains uncertain because the mutation introduced into the HTLV-1 molecular clone to ablate p13 also affected the HBZ gene.…”

Human T-cell leukemia/lymphoma virus type 1 nonstructural genes and their functions

“…Although p13 II is targeted primarily to mitochondria in the cell types tested so far (HeLa, fibroblasts, T cells) (Ciminale et al, 1999;D'Agostino et al, 2005b) (Figure 4a), it can occasionally be detected in the Functions of HTLV-1 p12 I , p13 II , and p30 II proteins C Nicot et al nucleus . The subcellular localization of p13 II might therefore be influenced by its expression levels and the physiological status of the cell.…”

Mitochondria as a Favourite Organelle for Invading Viruses

“…MMP (Δψm) is highly regulated process controlled by a different complex network of signaling pathways that involves both endogenous (e.g. pro-and anti-apoptotic Bcl-2 family proteins, p53, kinases, phosphatases, lipid second messengers [40][41][42][43][44][45][46], ROS, Ca 2+ overload as well as exogenous factors (e.g. viral proteins, toxins, pro-oxidants [29,[47][48][49][50].…”