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HTLV-1: Raising Awareness of a Deadly, Hidden Virus

Pooja Jain, PhD, MS
Pooja Jain, PhD, MS, professor, Department of Microbiology & Immunology and Department of Neurobiology & Anatomy

By Nancy West 

If you’ve never heard of human T lymphotropic viruses (HTLVs) or human T cell leukemia virus type 1 (HTLV-1), you aren’t alone. This rare, cancer-causing retrovirus is an ancient cousin of HIV with the ability to transform human T cells. Because it is a retrovirus, it can integrate its genetic material into a person’s DNA and live there forever. As a result, it can cause a chronic, lifelong viral infection, usually without any symptoms, that can lie dormant in the human body for 40 or more years.

During this time, it is estimated that 5% of people with HTLV infection will develop adult T cell leukemia or lymphoma (ATLL). By the time it causes symptoms and is diagnosed, the cancer is widespread and aggressive, and the infected person may only have six months to two years to live. That’s why Pooja Jain, PhD, MS, a professor in the College of Medicine’s Department of Microbiology & Immunology and Department of Neurobiology & Anatomy, is on a mission to raise awareness of this insidious virus.

“Compared to other cancer-causing viruses — such as Epstein-Barr, herpes, and hepatitis B and C — HTLV-1 has the highest potential of causing cancer in the people it infects,” says Jain. “Most oncoviruses have a 0.3 to 1% chance of causing cancer, while HTLV-1 has a 5% chance.”

Experts estimate that 10 to 20 million people worldwide have an HTLV-1 infection, but infection rates vary widely. In North America, about 300,000 people are known to be infected. But in other parts of the world, one-third or more of the population is infected, including specific parts of Brazil, Japan, Africa, South America, Australia and the Caribbean.

HTLV-1 is transmitted most often through breastfeeding. In endemic regions, around 20 to 30% of HTLV-1-infected mothers transmit the virus to their infants in this way. The virus is also transmitted through sexual contact, needle sharing and unsafe blood transfusions.

In addition to cancer, HTLV-1 can also cause a progressive inflammatory disease of the nervous system called HTLV-associated myelopathy and tropical spastic paraparesis (HAM/TSP).

“This virus is able to cross the blood-brain barrier and enter the central nervous system,” explains Jain, who has been conducting HTLV research for 23 years. “When it enters the nervous system, it attacks the myelin sheath of neurons, causing a disease that is very similar to multiple sclerosis. So the same virus in the blood that can cause lymphoma can also cause myelopathy in the brain.”

The Phenomenon of Immune Exhaustion

Jain was intrigued by the extensive immune response she saw in patients who have HAM disease. “These patients develop a very strong immune response that is incapable of killing the virally infected cells,” she notes. “This leads to the phenomenon of immune exhaustion. Our immune system is constantly under attack by the virus antigen, but the dose of antigen is not powerful enough for our immune system to kill the infected cell. As a result, there is a low-grade inflammation that goes on and on. Eventually, the time comes when the immune system becomes so crippled that the patient will develop ATLL or HAM.” She adds, “My lab was able to establish very early that this phenomenon of immune exhaustion does not only work in cancer, but also in neuroinflammation.”

Sharrón (Ronni) Manuel, MD, PhD ’13
Sharrón (Ronni) Manuel, MD, PhD ’13

Key to this research was Sharrón (Ronni) Manuel, MD, PhD ’13, one of the first Drexel Woman One Scholarship recipients, who worked in Jain’s lab from 2006 to 2011. “Ronni was sampling patients with a high level of neuroinflammation,” Jain notes. “We found that they had very high levels of the PD-1 molecule that acts like a brake on the immune system and can cause immune exhaustion.”

“We saw that there were various immune cell markers, especially on dendritic cells, that were either up- or down-regulated depending on their role in the immune system,” explains Manuel. “A lot of inflammatory markers were up-regulated in those patients with disease compared to the asymptomatic carriers, which told us that there was a heightened immune or inflammatory response in those patients.”

She continues, “PD-1 is one of the most effective receptor targets to block in cancer therapy. When PD-1 binds to PDL-1 or PDL-2, it tells the T cells to slow down or stop their attack. If certain cancer cells up-regulate that, then the T cells are not going to attack, and those cancer cells continue to grow and attack the body. By therapeutically blocking the PD-1/PDL-1/2 interactions, the brakes from the immune system are removed, restoring normal T cell function, leading to antitumor responses. We saw that PDL-1 was up-regulated in the cells of the HTLV disease population compared to the asymptomatic carriers. If we could somehow block that response in a vaccine, we could control the disease progression, which was our ultimate goal.”

A Dual Vaccine Approach

Based upon Manuel’s thesis observations, the Jain Lab proceeded to test a dual vaccine approach — blocking the PD-1 molecule but also combining with new epitopes for vaccine purposes.

Manuel Continues Immunology Research

Inspired by her mentor, Pooja Jain, PhD, MS, Sharrón (Ronni) Manuel, MD, PhD ’13, has continued her immunology research.

“Pooja was a terrific mentor,” emphasizes Manuel. “Seeing her drive and enthusiasm really encouraged me to continue doing research. She provided me with a truly diverse, hands-on experience where I was able to learn the ins and outs of conducting research projects. I also traveled and presented at international conferences. It was an honor to receive the Young Investigators Award for my presentation at an HTLV conference in Japan. All these experiences were invaluable to me.”

Now a reproductive endocrinology and infertility physician at HRC Fertility, and an assistant professor at the University of Southern California, she focuses on how the immune system affects reproduction, with interests in PCOS, endometriosis, ovarian aging, pregnancy loss and miscarriage.

“This combination acts like a double-edged sword — when you take the brake off, the existing immune system works, and then when you put new epitopes on the T cell, you bring in fresh immunity, and the combination of the two helps to eradicate neuroinflammation in virus-infected cells,” Jain explains. “This is what I consider to be the major contribution from our lab — studying and establishing this phenomenon in neuroinflammation caused by HTLV-1 and also testing a new idea for immunotherapy or vaccine against HTLV-1,” she says.

Manuel adds, “Through our research, we hoped to find a way to keep HTLV-1-infected patients asymptomatic as much as possible instead of progressing to disease.”

At the same time, other researchers in Jain’s lab were studying the HTLV-1 mechanism for oncogenesis, which involves T cell transformation. HTLV-1 has a very powerful oncoprotein capable of triggering the leukemia genesis process. Jain’s lab discovered a new target called MEF-2 — myocyte enhancer factor 2.

“We found that MEF-2 cooperates with the viral factor and aids the process of T cell transformation,” says Jain. “So, our lab was able to decipher immune mechanisms as well as devise a novel target for chemotherapy.”

Currently, Jain’s lab is testing a small molecule inhibitor that belongs to a proven group of anticancer molecules. She is hoping to take this to clinical trials, depending upon the availability of funding.

Raising Awareness: June 2026 IRVA Conference

Outside the lab, Jain is working tirelessly to increase awareness of HTLV-1 to fulfill her role as the secretary of the International Retrovirology Association (IRVA) since 2023. Now she is also serving as chair of the 22nd BiennialInternational Conference on HumanRetrovirology: HTLV and Related Viruses, to be held in Philadelphia on June 3-6, 2026.

“People from around the world who are experts in HTLV-1 diagnosis, translation, clinical trials and basic science research will be invited to speak at this conference,” says Jain. “We will also invite patients to share their experiences of living with HTLV-1.”

She adds, “This conference will cover some of the most important advances in discovery research, molecular and immunological pathogenesis, pre-clinical models, epidemiology, diagnostics, prevention, vaccinology and therapeutics.”

Engaging With the Community

In the Philadelphia area, Jain has been engaged in various community outreach activities. “We are finding many high-risk communities within Philadelphia and nearby areas where viral-infected patients could exist, but no one knows about them,” she states. “I think there are many more cases of HTLV-1 in the U.S. than we’re aware of. It’s all about surveillance — and there is no real surveillance of HTLV-1 in this country. If we do more, I’m sure we’re going to find a lot more cases that we can treat before the patients are in the advanced stages of ATLL. Because this cancer is considered a rare disease in the U.S., we haven’t been making the progress we should be making,” she emphasizes. “My hope is that this conference will help to change that.”

Jain is also very engaged in working with African American communities living in Philadelphia who are represented by the African Cultural Alliance of North America (ACANA). “They are willing to work with us to educate their communities about the risk of the viruses being transmitted primarily through breastfeeding, but also by sexual intercourse and intravenous drug use,” she says.

Jain notes that in some countries, such as Brazil, where the incidence of HTLV-1 is much higher, there is a government mandate to screen every pregnant patient for this virus. Those who are found to be infected are prohibited from breastfeeding and are given baby formula by the government.

“Brazil has become a superstar county in taking very strong measures to prevent the transmission of HTLV-1, and our hope is that this will spread to other places where the virus is present,” says Jain.

She also notes that Japan has many immunotherapy vaccine trials in progress because they have more HTLV-1 patients, as well as government support.

Drexel Initiates HTLV-1 Screening in Philadelphia

In Philadelphia, Drexel University College of Medicine has recently begun collaborating with the Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University and ACANA. More importantly, Jain’s lab — in collaboration with the Jefferson community outreach unit, clinicians and ACANA — have earned a $100,000 pilot grant to conduct mobile screening in high-risk communities. Jain intends to expand this initiative to other cities within the U.S.

“If someone tests positive for HTLV-1 in the Philadelphia area, we refer them to our collaborators at Jefferson who have been treating HTLV-1 patients,” says Jain. “If a patient is diagnosed with an HTLV-1- related myelopathy, we refer them to the University of Pennsylvania Neuroscience Unit.”

She adds, “We need to educate health systems about who could potentially be at risk. Then it will be up to the health care professionals to educate these patients and ask them to undergo screening. This will be critical to our success in reaching more patients before it’s too late to help them.”

Internationally, interest in HTLV-1 and related viruses has increased significantly in the last six years, according to Jain. Researchers are making progress in vaccine development, and they are seeing the potential to repurpose some existing antiretroviral therapies.

“More — much more — needs to be done,” says Jain. “There remains an urgent need to expedite research and its funding; spread awareness; engage patients, communities, policymakers, the World Health Organization and pharmaceutical industries; and make sure that the voice of people living with HTLV is heard.”