Pathogenesis and Immunity - Human T-Lymphotropic Viruses

Pathogenesis and Immunity

HTLV-1 is a lymphotropic virus. The HTLVs are distinguished from HIV as they cause lymphoproliferative disorder, whereas HIV causes lymphocytosis. It enters the host by sexual intercourse, breast feeding, or blood transfusion.

◗ Pathogenesis of HTLV infection

After entry in humans, the virus spreads through circulation and infects the CD4 helper and DTH (delayed-type hypersensi-tivity) T cells. These T cells are most commonly present in the skin as well as in the neurons. Recent evidences show that glu-cose transporter (GLUT-1) is a supportive receptor for HTLV-1 cell entry. The ubiquitous distribution of GLUT-1 may help explain the viral tropism of HTLV-1.

HTLV predominantly infects and integrates lymphocytes. Once the infection is transmitted, the tax gene (which encodes Tax protein) transactivates the cellular genes for T-cell growth factor and IL-2 and their receptors, all of which activate growth in the infected cells. The viruses in the infected cell may remain latent or may replicate slowly for many years and may also induce the clonal outgrowth of particular T-cell clones.

There is a long latency period of approximately 30 years before the onset of leukemia. Although the exact mechanism of viral pathogenesis of T-cell leukemia that occurs in 3–5% of individuals is not known, in vitro studies have shown that the tax gene plays an important role.

It has also been demonstrated that HTLV can spread by cell-to-cell contact without replication, but it is not clear how HTLV crosses the blood–brain barrier to cause neurological sequelae of HTLV infection.