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 Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

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: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>