Research Snapshot: A detailed look at HTLV-1, the retrovirus that causes T-cell Leukemia

Retrovirus replication remains an intriguing enigma to researchers. Scientists continue to unearth more and more insight, but the process is still poorly understood.

It is generally believed that virus particles need to be fully formed to transmit a virus. But a recent study by researchers in the Academic Health Center’s Institute for Molecular Virology (IMV) shows this may not be the case.

“It is quite surprising a virus would primarily produce virus particles that have structural defects,” said Louis Mansky, Ph.D., lead author of the study, director of the IMV, and professor in the School of Dentistry. Mansky is also a Masonic Cancer Center member.

Mansky’s team studied human T-cell leukemia virus type 1 (HTLV-1), which causes T-cell leukemia. Using the cutting edge technology of cryo-electron microscopy, researchers were able to capture detailed images of HTLV-1 particles. The researchers were surprised to find most particles were quite different. They varied in size and structure, many even lacking organized cores.

The main takeaway: The virus has physical defects that appear to render it non-infectious.

The study was recently published in the Journal of Virology.

“Why would a virus evolve to produce incomplete virus particles? This is currently a mystery, but the fact it does it this way means it must offer a selective advantage to the virus, perhaps to help evade the immune system,” Mansky said.

RNA, which initiates virus replication, is located in the “capsid” or particle core. With so many particles lacking a fully-formed capsid, it raises questions about how the virus spreads among infected individuals. More importantly, it suggests that intervening with core formation could block virus transmission.

That opens the door to new potential drug therapies, vaccines or other interventions.

“To fight these diseases, we need to understand how they work,” Mansky said. “Right now, we don’t have effective therapies for treating HTLV-1 infection, but gaining a deeper understanding of basic viral replication should help in identifying targets for therapeutic intervention. Our findings help provide important clues to direct the next steps, and could lead us to a potential treatment or preventative for human leukemia.”

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