Novel approach to track HIV infection

August 18, 2017
HIV infecting a human cell. Credit: NIH

Northwestern Medicine scientists have developed a novel method of tracking HIV infection, allowing the behavior of individual virions—infectious particles—to be connected to infectivity.

The findings could help lead to the development of novel therapies for HIV prevention and treatment by providing a deeper understanding of the mechanisms of HIV's lifecycle.

The paper was published August 7 in Proceedings of the National Academy of Sciences.

It has become routine to visualize the movement and progression of individual virions in , but the relevance of these observations was previously unclear, as many virions are defective or do not progress to make further copies of themselves.

"This approach—and the ability to say 'that virion infected that cell'—will help bring clarity to the field," said principal investigator Thomas Hope, a professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. "It allows us to understand what the virus really needs to do to infect a cell. It gives us new details, like where in the cell it happens and the timing of specific events. The more we know about the virus, the better our chances are to stop it."

During the course of infection, HIV fuses onto a target immune cell and delivers its capsid—a cone that holds the genetic material of the virus—into the cell's cytoplasm. From there, the capsid disassembles through a process called "uncoating," which is crucial to the synthesis of viral DNA from its RNA genome and the hijacking of the cell's functions.

But the specific details of uncoating have been controversial, with two groups of thought. One believed that uncoating takes place late at pores, allowing factors to enter the nucleus. A second camp showed data suggesting that uncoating takes place early and in the cytoplasm.

In part, the uncertainty persisted because previous methods in HIV research have been unable to distinguish between viral particles that actually lead to infection of the cell, and those that are irrelevant.

In the current study, the team of scientists used a novel live-cell fluorescent imaging system that allowed them for the first time to identify individual particles associated with infection.

In this case, they utilized the approach to monitor how the HIV capsid uncoats in the cell at the individual particle level. They demonstrated that uncoating leading to infection occurs early in the cytoplasm, around 30 minutes after cell fusion.

The finding is just one example of novel discoveries about HIV that might now be possible with the imaging system.

"Being able to connect infectivity of individual particles and how they behave in the cell to infection—which is what we really care about—is going to have a big impact on the field," Hope said. "The system can now be used to resolve other controversies in HIV biology and to determine which potential targets for drug development are most relevant."

The study has implications in the wider field of virology research as well.

"Theoretically, you could apply this technique to the study of any fluorescently-tagged virus," explained first author João Mamede, a post-doctoral fellow in Hope's laboratory.

In future projects, Hope's research team plans to continue to leverage the method to study infection in later stages of the HIV lifecycle.

"We want to understand all the details, from when the virus fuses, to the point where it integrates and starts to make new viruses, to the last phase," explained Hope, also a professor of Obstetrics and Gynecology and of the McCormick School of Engineering. "We need to understand what's going on, so we can find the Achilles' heel of the and use it as a drug target."

Explore further: Protein critical to early stages of cellular HIV infection identified

More information: João I. Mamede et al. Early cytoplasmic uncoating is associated with infectivity of HIV-1, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1706245114

Related Stories

Protein critical to early stages of cellular HIV infection identified

August 8, 2017
When a virus enters a cell, one of the first steps in the process of infecting that cell is removal of the protein coat that surrounds the virus's genetic material. The virus can then produce DNA from its own genes and insert ...

Study demonstrates how Zika virus rewires and repurposes invaded cells

March 30, 2017
New research reveals a high-resolution view of the Zika viral life cycle within infected cells and shows dramatic changes in the cell's architecture throughout the infection process. This novel perspective may lead to the ...

Scientists reveal new phase of HIV infection

December 16, 2015
Researchers at the University of Massachusetts Medical School have identified a new life cycle stage in HIV infection, thanks to a novel technique they developed to take images of intact infected cells. They've shown that ...

Researchers track HIV in real time as it infects and spreads in living tissue

June 9, 2016
By watching brightly glowing HIV-infected immune cells move within mice, researchers at the Icahn School of Medicine at Mount Sinai have shown how infected immune cells latch onto an uninfected sister cell to directly transmit ...

Recommended for you

Groundbreaking investigative effort identifies gonorrhea vaccine candidates

September 19, 2017
Researchers at Oregon State University have identified a pair of proteins that show promise as the basis for a gonorrhea vaccine.

Snail fever progression linked to nitric oxide production

September 14, 2017
Bilharzia, caused by a parasitic worm found in freshwater called Schistosoma, infects around 200 million people globally and its advance can lead to death, especially in children in developing countries.

Systems analysis points to links between Toxoplasma infection and common brain diseases

September 13, 2017
More than 2 billion people - nearly one out of every three humans on earth, including about 60 million people in the United States - have a lifelong infection with the brain-dwelling parasite Toxoplasma gondii.

Study clears important hurdle toward developing an HIV vaccine

September 13, 2017
An international team of researchers has demonstrated a way of overcoming one of the major stumbling blocks that has prevented the development of a vaccine against HIV: the ability to generate immune cells that stay in circulation ...

As 'flesh-eating' Leishmania come closer, a vaccine against them does, too

September 13, 2017
Parasites that ulcerate the skin, can disfigure the face, and may fatally mutilate its victim's internal organs are creeping closer to the southern edges of the United States.

Promising clinical trial results could give doctors a new tool against drug-resistant strains of malaria parasite

September 13, 2017
Tulane University researchers have developed a new drug that is effective against non-severe cases of malaria, according to results from an FDA-supervised clinical trial published in the latest issue of The Lancet Infectious ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.