Renewed research focus on the human T-cell leukemia virus

Human T-cell leukemia virus

Human T-cell leukemia virus
Photo courtesy of AJC1 on Flickr

Human T-cell leukemia virus-1(HTLV-1) is the only known retrovirus to directly cause cancer in humans. Infection with this retrovirus affects millions of people worldwide, but currently there is neither a targeted antiretroviral therapy nor a vaccine available. HTLV-1 was isolated and characterized in the NCI intramural program in 1980, but the discovery was rapidly overshadowed by the AIDS epidemic.

Infection by this virus has become a neglected condition, and only palliative treatments are available to the 10 to 20 million HTLV-1 infected individuals living mostly in resource-deprived countries. November 10, 2018, has been declared HTLV-1 Day by the International Retrovirology Association to focus research efforts around the pathogen.

In humans, HTLV-1 is transmitted through breastfeeding, transplacentally, sexually and by blood transfusion and organ transplants and is known to cause a lethal cancer, adult T-cell leukemia/lymphoma (ATLL). HTLV-1 infection can also lead to a plethora of inflammatory conditions such as uveitis and dermatitis, including the neurological degenerative condition designated as tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) that results in paralysis of the lower limbs.

The recent description of a high prevalence of the subtype HTLV-1C in the underserved Aboriginal communities of the Northern Territory of Australia has revived interest in research around the retrovirus. In these communities, HTLV-1C infection is associated not only with ATLL and TSP/HAM but also with a high mortality in people in their mid-40s, due to lung inflammation, bronchiectasis and infectious diseases.

In CCR’s Lymphoid Malignancies Branch, Thomas Waldmann, M.D., defined molecular abnormalities of the common gamma cytokine Jak/Stat signaling pathway in ATLL and is translating this discovery with an ongoing trial of a Jak inhibitor in patients with this disorder. The branch continues to focus on translating fundamental biologic insights into novel treatment of human B and T-cell lymphoid malignancies, and more clinical trials for treatment of ATLL are currently planned or underway.

In CCR’s Vaccine Branch, investigators are determining whether infection with subtypes HTLV-A and HTLV-1C causes different inflammatory profiles in animals and humans. An understanding of the inflammatory profiles induced by type A and C infection in humans, when paired with equivalent results in macaques, may guide the choice of anti-inflammatory drugs and provide a suitable animal model for testing their efficacy in preventing the inflammation associated with HTLV-1 A and C.

“The discovery of novel preventive or therapeutic remedies for this retrovirus could relieve not only the suffering of HTLV-1 infected individuals but also augment understanding of other chronic infections with cancer viruses as well as unexpected viral strategies that are used to hijack a host organism,” says Genoveffa Franchini, M. D., Senior Investigator in the CCR Vaccine Branch who has conducted pioneering work on the retrovirus.

Summary Posted: 11/2018