Health & Medicine
HIV Infection: New Phase Revealed By UMMS Scientists
Matt Hoffman
First Posted: Dec 16, 2015 03:03 PM EST
A new life cycle stage in HIV infection has been uncovered by a team scientists at the University of Massachusetts Medical School using a novel technique in imaging, developed by the team to take images of infected cells. This phase discovered was dubbed the "intra-nuclear migration stage" by Abraham Brass, the principal investigator in the study.
The intra-nuclear migration stage relies on CPSF6, a human protein, to guide HIV through the nucleus of the host cell and position it where it seeks to settle itself: within active genes.
"This study reveals an important stage and mechanism in HIV infection that was previously unappreciated," Brass said. "It's important to know more about these early infection events so we can come up with ways to stop the virus from becoming part of our DNA and infecting us for life."
This discovery was made using ViewHIV, an imaging technique developed by the UMMS team, consisting of Brass, Jill Perreira and Chris Chin of UMMS, and Eric Feeley of Duke University, specifically for this study. Using ViewHIV, the team monitored the migration of the virus, which is made up of a protein capsule, or caspid, that contains the DNA of HIV, as it moves around the nucleus after passing through the nuclear membrane.
Scientists had previously been unable to generate and produce solid images of HIV while it was inside the nucleus. This limitation prevented direct insight into HIV's transit across the nuclear membrane. Most information had been obtained indirectly through molecular biology and biochemistry methods, normally used to evaluate large cell populations.
"There are certain characteristics of a virus you can only learn about by keeping it intact and seeing it in action in single cells," Perreira, a co-lead author on the study said. "Researchers have been studying HIV for 30 years, but we still didn't have a really good way to look inside infected cells. We thought that if we could just see what's going on, then we could get a better idea of what the virus is doing and how to stop it."
ViewHIV takes a sensitive type of fluorescence in situ hybridization (FISH), and pairs it with a monoclonal antibody that binds to the HIV caspid. The process uses a protease, an enzyme that breaks down proteins into amino acids, which tags the caspid with a fluorescent antibody, allowing the team to see it in the nucleus. This was key in preparing samples, according to Brass.
The team used ViewHIV to watch the viral caspid's role in the virus's ability to both enter and navigate through the host cell's nucleus. They watched it as it moved through the cytoplasm, across the nuclear membrane and into the host cell's DNA. The team saw that, contrary to previous beliefs, HIV doesn't completely shed its caspid before it enters the nuclear pore complex.
The caspid uses the proteins CPSF6 and TNPO3 to enter the nucleus. Without the proteins' help, the virus gets stranded outside the edge of the nucleus, according to a news release. CPSF6 normally modifies newly made RNA, and finds active genes once it's in the nucleus. The virus hitches a ride along with CPSF6, and is imported across the nuclear membrane by TNPO3. Without just one of these two, the virus cannot make the journey, and instead makes its way to less active gene regions of the cell.
"We believe ViewHIV is going to be a great tool for unlocking the mechanisms that govern the early state of HIV's life cycle," Brass said. "With our technique we can better determine how HIV establishes itself into our DNA and develop new ways to stop that from happening."
Related Articles
HIV Vaccine: Study Provides Insight Into Possible Development
HIV Particles Don't Directly Cause AIDS, Immune Cell Response Does
For more great science stories and general news, please visit our sister site, Headlines and Global News (HNGN).
See Now:
NASA's Juno Spacecraft's Rendezvous With Jupiter's Mammoth Cyclone
TagsHIV, HIV infection, University of Massachusetts, University of Massachusetts Medical School, UMMS, Abraham Brass, Jill Perreira, Chris Chin, Eric Feeley, Duke University, ViewHIV, CPSF6, TNPO3, DNA, RNA, Caspid, Nuclear Membrane, Fluorescence In Situ Hybridization, Monoclonal Anitbody, Protease, cytoplasm, nuclear pore complex ©2024 ScienceWorldReport.com All rights reserved. Do not reproduce without permission. The window to the world of science news.
More on SCIENCEwr
First Posted: Dec 16, 2015 03:03 PM EST
A new life cycle stage in HIV infection has been uncovered by a team scientists at the University of Massachusetts Medical School using a novel technique in imaging, developed by the team to take images of infected cells. This phase discovered was dubbed the "intra-nuclear migration stage" by Abraham Brass, the principal investigator in the study.
The intra-nuclear migration stage relies on CPSF6, a human protein, to guide HIV through the nucleus of the host cell and position it where it seeks to settle itself: within active genes.
"This study reveals an important stage and mechanism in HIV infection that was previously unappreciated," Brass said. "It's important to know more about these early infection events so we can come up with ways to stop the virus from becoming part of our DNA and infecting us for life."
This discovery was made using ViewHIV, an imaging technique developed by the UMMS team, consisting of Brass, Jill Perreira and Chris Chin of UMMS, and Eric Feeley of Duke University, specifically for this study. Using ViewHIV, the team monitored the migration of the virus, which is made up of a protein capsule, or caspid, that contains the DNA of HIV, as it moves around the nucleus after passing through the nuclear membrane.
Scientists had previously been unable to generate and produce solid images of HIV while it was inside the nucleus. This limitation prevented direct insight into HIV's transit across the nuclear membrane. Most information had been obtained indirectly through molecular biology and biochemistry methods, normally used to evaluate large cell populations.
"There are certain characteristics of a virus you can only learn about by keeping it intact and seeing it in action in single cells," Perreira, a co-lead author on the study said. "Researchers have been studying HIV for 30 years, but we still didn't have a really good way to look inside infected cells. We thought that if we could just see what's going on, then we could get a better idea of what the virus is doing and how to stop it."
ViewHIV takes a sensitive type of fluorescence in situ hybridization (FISH), and pairs it with a monoclonal antibody that binds to the HIV caspid. The process uses a protease, an enzyme that breaks down proteins into amino acids, which tags the caspid with a fluorescent antibody, allowing the team to see it in the nucleus. This was key in preparing samples, according to Brass.
The team used ViewHIV to watch the viral caspid's role in the virus's ability to both enter and navigate through the host cell's nucleus. They watched it as it moved through the cytoplasm, across the nuclear membrane and into the host cell's DNA. The team saw that, contrary to previous beliefs, HIV doesn't completely shed its caspid before it enters the nuclear pore complex.
The caspid uses the proteins CPSF6 and TNPO3 to enter the nucleus. Without the proteins' help, the virus gets stranded outside the edge of the nucleus, according to a news release. CPSF6 normally modifies newly made RNA, and finds active genes once it's in the nucleus. The virus hitches a ride along with CPSF6, and is imported across the nuclear membrane by TNPO3. Without just one of these two, the virus cannot make the journey, and instead makes its way to less active gene regions of the cell.
"We believe ViewHIV is going to be a great tool for unlocking the mechanisms that govern the early state of HIV's life cycle," Brass said. "With our technique we can better determine how HIV establishes itself into our DNA and develop new ways to stop that from happening."
Related Articles
HIV Vaccine: Study Provides Insight Into Possible Development
HIV Particles Don't Directly Cause AIDS, Immune Cell Response Does
For more great science stories and general news, please visit our sister site, Headlines and Global News (HNGN).
See Now: NASA's Juno Spacecraft's Rendezvous With Jupiter's Mammoth Cyclone