Cell-to-cell transmission in the pathogenesis of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis

Abstract

Virus transmission is an important key factor for understanding the pathomechanism(s) of virus-related neurological diseases. In the past, cell-free transmission was believed to be a major route of virus spread for almost all viruses. However, attention was paid to “cell-to-cell transmission” in the 1960s. Cell-to-cell transmission appears to be more effective, as progeny viruses do not have to encounter antibodies. Although this mode of virus transmission was first highlighted in subacute sclerosing panencephalitis caused by a variant of measles virus, human T-lymphotropic virus type 1 (HTLV-I) also utilizes cell-to-cell transmission. The transmission is undergone through so-called “virological synapses”, a structure first described in HTLV-I. Cell contact induces polarization of the cytoskeleton of the infected cells to the cell–cell junction. HTLV-I core (Gag protein) complexes and the HTLV-I genome accumulate at the cell–cell junction and are transferred to the uninfected cell. The intracellular cyclic adenosine monophosphate regulates the efficiency of intercellular HTLV-I transmission under the control of expression phosphorylated vasodilator- stimulated phosphoprotein.