A New Virus
HTLV-III, the presumptive AIDS virus, belongs to the family of retroviruses known as human T-cell leukemia-lymphotropic viruses (HTLV). This group of agents includes HTLV-I, which is strongly associated with an adult form of leukemia-lymphoma that is uncommon in the United States but found more frequently in other parts of the world (including Japan, the Caribbean, parts of Africa, and South and Central America); and HTLV-II, which was isolated from a patient with hairy cell leukemia. The American groups report that while the HTLV-III virus shares some important similarities with other retroviruses—particularly the other two known HTLV viruses (as well as bovine leukemia virus)—HTLV-III has some unique properties. They conclude that HTLV-III is a new virus, rather than a virus that arose by small changes in known viruses already present in the population.
Dr. Wong-Staal of NCI said, “Although we recognize several key features of the virus structure from studies of related viruses, other features of the virus are new and unique to this virus. We speculate that some of these unusual features may be involved with mechanisms of disease.”
Dr. Haseltine described the structure of the HTLV-III virus as “surprising”. “It is similar in many respects, and in fundamental respects, to other retroviruses—particularly the human leukemia viruses and a close relative, the bovine leukemia virus,” he said.
Like other retroviruses, HTLV-III is an RNA virus that contains a set of proteins (core proteins) that surround the RNA, uses a polymerase (reverse transcriptase) to convert RNA to DNA as part of its life cycle, and is surrounded by an outer envelope. However, while the organization and structure of the core proteins and polymerase genes generally resemble those features in other retroviruses (particularly HTLV-I and HTLV-II), the organization of the key envelope genes of HTLV-III appears to be unique.
Dr. Lee Ratner, a researcher at NCI and the first author on the American group’s report in the January 24 issue of Nature, said that the envelope gene “was not where we expected it to be” and that the gene for the envelope protein is much larger than similar genes in other retroviruses.
A major surprise came from an analysis of a genetic region which is “bi-functional, encoding both an envelope gene and a gene called lor we had previously recognized in HTLV-I, HTLV-II, and bovine leukemia virus,” Dr. Haseltine told GEN. “The lor gene of the virus overlaps the envelope gene; one genetic region [of the HTLV-III virus] has two distinct functions in this virus—it encodes both the envelope and lor proteins.” In the human leukemia viruses, the envelope and lor genes are separate genes.
Researchers believe the lor gene is important for the growth of the virus itself, as well as for determining the effects of virus infection on the target cells. Both the human leukemia viruses and the AIDS virus infect the same kind of immune cells—the T-4 population of T cells (helper T cells). The outcomes of the infections are markedly different; while the human leukemia virus immortalizes the T cells and cause uncontrolled growth, the AIDS virus kills these cells and causes the failure of the immune system that characterizes AIDS.
“We’re interested in how the virus works, why it kills the same cells that the leukemia viruses immortalize,” said Dr. Wong-Staal.
“There’s something quite specific and interesting about the killing mechanism that has to be understood,” Dr. Haseltine said. He says that the action of the lor gene might be responsible for determining the different effects of the viruses in the HTLV family on the same type of cell. If this is the case, then a detailed analysis of how the gene products work could be important in the development of new therapeutic approaches for treatment of AIDS infections.