Nancy Mueller
"We should be thinking of primary prevention," said Mueller during the lecture held on May 4 in Snyder Auditorium. "We're really not doing our job."
Mueller has served as Associate Director for Population Sciences at the Dana Farber/Harvard Cancer Center since 2000. She has studied the human T-lymphotropic virus type 1 (HTLV-1) for much of her career. The virus causes a type of cancer called adult T-cell leukemia/lymphoma (ATL) and an associated neurological syndrome in about five to six percent of carriers.
"It's important because we can stop it," she said. "We have the tools. We know who to intervene with. We should be able to eliminate this virus. If we really did the primary prevention, this virus would die. It can't keep up its reproductive rate."
Although much has been learned about the virus since it was discovered in 1980, little attention has been paid to preventing its spread. The virus is thought to be very old, and the majority of infected people never develop symptoms.
HTLV is not readily transmitted, except through blood transfusions. Major transmission routes are prolonged breastfeeding and sexual exposure. IV drug users are also at risk. Infection is more efficient in people with a high viral load, which appears to be more common in groups with poorer health and nutrition.
Mueller suspects that attention was diverted away from HTLV-1 by the discovery of the AIDS virus HIV, just a few years after the cancer-causing virus was identified. That was to be expected, she said, since HIV is a worldwide pandemic.
Another reason for the scant attention is that HTLV does not loom large over the U.S. Most carriers of the virus live in Jamaica, southern Japan, sub-Saharan Africa, and, in the U.S., in pockets of immigrants, most notably in New York City and Miami.
"HTLV-1 doesn't have a domestic constituency," Mueller said. "Our infection in this country is really among immigrants. Many are not documented. They're not organized. And the numbers are small here."
Just which carriers of the virus will get sick depends on a number of factors, such as viral load. But other factors seem at play as well. For example, a study that Mueller co-founded looked at 2,046 carriers in Japan and found six cases of adult T-cell leukemia/lymphoma over a 16-year follow-up. The ages of death ranged from 66 to 83 years.
Yet data from an National Cancer Institute study in Jamaica found that most victims were dying in their 40s and 50s, she said. It depends on where you live and what the conditions are, she said.
Mueller called for more cohort studies designed to determine the natural history of the infection and to identify risk factors in blood.
HTLV-1 itself is a small virus, with only about 9,000 genetic base pairs, she said. One gene, called "tax," is the "mastermind gene" that can cause the virus infection to result in cancer. While virus-specific T-cells seek to control the proliferation of the cells that express this protein, tax expression is sometimes turned off in infected cells, allowing them to evade the circulating T cells.
At the same time, HTLV-1 is genetically stable at the population level, meaning it mutates very little, unlike HIV. As a result, strains are often the same or nearly the same, no matter where the carriers live.
HTLV-1 evolved alongside the simian T-lymphotropic virus (STLV), a built-in animal model. "This is a very ancient infection," she said. As a result, it is an attractive research model, she said.
While HTLV-1 infection can't be cured, Mueller said that those who test positive can be monitored and can be educated so that they won't pass on the virus to others. It is also a challenge for basic scientists to develop interventions to reduce viral load and eliminate pre-cancerous cells in infected persons at high risk.
—ML
Copyright, 2009, President and Fellows of Harvard College
