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 Antibiotic effective against drug-resistant bacteria in pediatric skin infections
17.02.2017 | University of California - San Diego

nachricht Tiny magnetic implant offers new drug delivery method
14.02.2017 | University of British Columbia

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>