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, 2019, 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 HIV and AIDS Malignancy BranchRobert Yarchoan, M.D., and colleagues have identified a drug that may help the treatment of HTLV-1 infection by targeting viral proteins that hamper both innate and adaptive host responses to the virus.

In CCR’s Vaccine Branch, Genoveffa Franchini, M.D., and colleagues have identified host innate and adaptive immune responses that inhibit HTLV-1 infection and is investigating 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. Dr Franchini’s group has also organized an international HTLV-1 workshop (sponsored by CCR) to be held on the NIH campus on April 2-3, 2020 with the goal to increase HTLV-1 awareness and identify unmet needs in HTLV-1 research.

“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.

Posted on Fri, 11/09/2018