Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Loyola study reveals how HIV enters cell nucleus

23.06.2016

Loyola University Chicago scientists have solved a mystery that has long baffled HIV researchers: How does HIV manage to enter the nucleus of immune system cells?

The discovery, reported in the journal PLOS Pathogens, could lead to effective new drugs to treat HIV/AIDS, said Edward M. Campbell, PhD, corresponding author of the study. Campbell is an associate professor in the Department of Microbiology and Immunology of Loyola University Chicago Stritch School of Medicine.


IV-1 viral cores (red) accumulate around the cell nucleus (blue) but remain unable to enter following depletion of the motor protein KIF5B.

Credit: Loyola University Chicago

HIV infects and kills immune system cells, including T cells and macrophages. This cripples the immune system, making the patient vulnerable to common bacteria, viruses and other pathogens that usually don't cause problems in people with healthy immune systems.

Once HIV enters a cell, it has to find a way to get inside the nucleus, the compartment that contains the cell's DNA. Many related viruses do this by waiting until the cell divides, when the protective membrane surrounding the nucleus breaks down. But HIV has the insidious ability to enter the nucleus in a non-dividing cell with an intact nuclear membrane. (This membrane also is known as the nuclear envelope.)

How HIV gets through the nuclear envelope has been a mystery. In part, this is because the HIV core (the protein shell that protects the HIV genome) is 50 percent larger than the pores in the envelope. These pores normally enable cellular proteins and other materials to go back and forth between the nucleus and the rest of the cell.

Campbell and colleagues discovered that a motor protein, called KIF5B, interacts with both the HIV-1 core and the nuclear pore in a way that allows HIV into the nucleus. Normally KIF5B transports various cargoes within the cell, away from the nucleus. But HIV hijacks KIF5B to serve a different purpose: It induces KIF5B to tear off pieces of the nuclear envelope and transport them away from the nucleus, thus making the pore wide enough for HIV to pass through. (The pieces that are torn off are proteins called Nup358.)

The discovery opens a potential new strategy for fighting HIV. Developing a drug that prevents KIF5B from disrupting nuclear pores would prevent HIV from sneaking into the nucleus without detection. This would give the immune system enough time to sound the alarm to attack and destroy HIV.

Cells have surveillance mechanisms to detect viruses, and their DNA, in the cytoplasm (the part of the cell outside the nucleus). But HIV typically can enter the nucleus before it is detected by these mechanisms. Trapping HIV in the cytoplasm would not only prevent an infection, it might also lead to HIV being detected and thus prompt an immune response.

"It's like making a bank vault harder to break into," Campbell said. "In addition to making the money more secure, it would increase the chance of sounding the alarm and catching the burglars."

###

The study was supported by a grant from the National Institute of Allergy and Infectious Diseases. It's titled "KIF5B and Nup358 cooperatively mediate the nuclear import of HIV-1 during infection."

In addition to Campbell, co-authors are Adarsh Dharan, PhD, (first author); Sarah Talley, MS; Abhishek Tripathi, PhD; and Matthias Majetshak, PhD; all of Loyola's Stritch School of Medicine; and Thomas J. Hope, PhD and João Mamede, PhD of Northwestern University Feinberg School of Medicine.

Media Contact

Jim Ritter
jritter@lumc.edu
708-216-2445

 @LoyolaHealth

http://www.luhs.org 

Jim Ritter | EurekAlert!

Further reports about: DNA HIV HIV-1 cell nucleus cytoplasm immune system nuclear envelope pores viruses

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>