Dustin Edwards

Human retrovirus research: HTLV-1

This page covers Dustin Edwards's earlier research on human retroviruses, on human T-cell leukemia virus type 1 (HTLV-1). Each published paper, chapter and conference abstract has a short plain-language summary of what it found, a link to its page on this site and a link to its DOI. The papers are grouped by theme, then listed by year. It is written for students and for anyone curious about the work; the papers themselves have the full detail. His current retrovirus work, on viruses of wild birds, is on the avian retroviruses page.

HTLV-1 in brief#

HTLV-1 is a retrovirus that infects T cells, a type of white blood cell. Most people who carry it never become ill, but it causes adult T-cell leukemia (ATL), an aggressive cancer that is hard to treat with chemotherapy. Like every retrovirus, HTLV-1 inserts a DNA copy of its genome into the chromosomes of the cells it infects, so an infected person carries it for life. The 3′ end of its genome holds several overlapping genes for small regulatory and accessory proteins: Tax, the protein that drives cancer, and the products of two reading frames called orf-I and orf-II, the proteins p12, p8, p13 and p30.

What the work showed#

Taken together, this work helped explain how HTLV-1 persists in the body for decades. The accessory proteins p12, p8 and p30 do several jobs for the virus: they change calcium levels inside the cell, adjust the signals a T cell receives through its T-cell receptor, reduce the display of viral pieces that lets the immune system recognize infected cells, and hold the viral tax and rex messenger RNAs in the nucleus. The virus does not need these proteins to grow in cells in a dish, but it does need them to set up and keep a long-term infection in a living host.

Tax turns up the gene for PCNA, a protein involved in copying and repairing DNA, and in doing so can interfere with DNA repair, which may help explain the genetic instability of HTLV-1-infected cells. And blocking an enzyme called geranylgeranyl transferase lowered the survival of HTLV-1-transformed cells in a way that did not depend on the tumor suppressor p53, which points to a possible route for treatment.

Publications by theme#

Each entry links to its page on this site, which has the full citation, the abstract and, where one can be shared, the PDF. The full list of papers across every research area is on the publications page.

Tax and cell transformation#

The orf-I and orf-II proteins: p12, p8, p13 and p30#

The orf-I reading frame makes p12, which can be cut to make p8. The orf-II reading frame makes p13 and p30.

Simian T-cell lymphotropic virus type 3 (STLV-3) is a virus of monkeys that is nearly identical to HTLV-3, the most recently discovered human member of the family. Because no HTLV-3-infected cell line exists, STLV-3 is the way to study what that branch of the family encodes.

The HTLV-1 molecular epidemiology database#

Reviews and chapters#

  • 2007. A chapter on RNA tumor viruses, using HTLV-1 as the model: its Tax protein acts on the controls of cell division and DNA repair, and that is how the virus transforms cells. RNA Tumour Viruses, The Cancer Handbook. DOI: 10.1002/9780470025079.chap06.pub2
  • 2011. A review of what was then known about the orf-I products p12 and p8 and the orf-II products p13 and p30: how they are made from spliced messenger RNAs, and their reported effects on gene expression, cell death, host cell activation, infectivity, transmission and immune responses. The review makes the central point that these proteins are not required for the virus to replicate in cell culture but do matter for infection in a living host. Orf-I and Orf-II-Encoded Proteins in HTLV-1 Infection and Persistence, Viruses. DOI: 10.3390/v3060861

HTLV-1 coinfection poster#

One conference poster, listed under Publications by its published title, concerned regulatory proteins in coinfection. No abstract was published with it, so it is listed here by title only, with no summary of findings.