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Genetic defect may confer resistance to certain viral infections

Date:
April 9, 2014
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
A rare genetic disease, while depleting patients of infection-fighting antibodies, may actually protect them from certain severe or recurrent viral infections new research suggests. Researchers found that HIV and influenza viruses replicate in the cells of people with congenital disorder of glycosylation type IIb (CDG-IIb) at a much lower rate than in healthy donor cells, creating fewer and less infectious viruses.

Viruses (blue and pink) must use host cells (green) to create more viruses that spread infection (top panel). CDG-IIb patients have defective glycosylation, the process of adding sugars to proteins, resulting in poor production of viruses that depend on this process, such as HIV and influenza (bottom panel). The scientists also show that viruses coming from the patients' cells (orange) are less infectious because of changes to their outer shields.
Credit: NIAID

A National Institutes of Health (NIH) study reports that a rare genetic disease, while depleting patients of infection-fighting antibodies, may actually protect them from certain severe or recurrent viral infections.

Researchers found that HIV and influenza viruses replicate in the cells of people with congenital disorder of glycosylation type IIb (CDG-IIb) at a much lower rate than in healthy donor cells, creating fewer and less infectious viruses. The study, published in The New England Journal of Medicine, was led by Sergio Rosenzweig, M.D., Ph.D., director of the Primary Immune Deficiency (PID) Clinic at the NIH's National Institute of Allergy and Infectious Diseases (NIAID).

In the study, the researchers diagnosed CDG-IIb in two siblings with severe development issues who were referred to the NIAID PID Clinic though the NIH Undiagnosed Diseases Program. CDG-IIb is extremely rare, with only one other case reported. The genetic defect of the disease disrupts glycosylation, or the process of attaching sugars to proteins. As a result, proteins called gamma globulins, which include infection-fighting antibodies, are unstable and persist at low levels in the patients' blood.

Interestingly, some viruses, including HIV and influenza, depend on glycosylation to form protective shields. The researchers showed that these viruses were less able to replicate or create protective shields because of the glycosylation defects in CDG-IIb cells. In comparison, adenovirus, poliovirus and vaccinia virus, which either do not rely on glycosylation or do not form protective shields, replicated normally when added to both CDG-IIb and healthy cells. This study suggests that modulating aspects of host glycosylation may be a strategy to control certain viral infections.


Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Materials may be edited for content and length.


Journal Reference:

  1. Mohammed A. Sadat, Susan Moir, Tae-Wook Chun, Paolo Lusso, Gerardo Kaplan, Lynne Wolfe, Matthew J. Memoli, Miao He, Hugo Vega, Leo J.Y. Kim, Yan Huang, Nadia Hussein, Elma Nievas, Raquel Mitchell, Mary Garofalo, Aaron Louie, Derek C. Ireland, Claire Grunes, Raffaello Cimbro, Vyomesh Patel, Genevieve Holzapfel, Daniel Salahuddin, Tyler Bristol, David Adams, Beatriz E. Marciano, Madhuri Hegde, Yuxing Li, Katherine R. Calvo, Jennifer Stoddard, J. Shawn Justement, Jerome Jacques, Debra A. Long Priel, Danielle Murray, Peter Sun, Douglas B. Kuhns, Cornelius F. Boerkoel, John A. Chiorini, Giovanni Di Pasquale, Daniela Verthelyi, Sergio D. Rosenzweig. Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections. New England Journal of Medicine, 2014; 140409140010003 DOI: 10.1056/NEJMoa1302846

Cite This Page:

NIH/National Institute of Allergy and Infectious Diseases. "Genetic defect may confer resistance to certain viral infections." ScienceDaily. ScienceDaily, 9 April 2014. <www.sciencedaily.com/releases/2014/04/140409204511.htm>.
NIH/National Institute of Allergy and Infectious Diseases. (2014, April 9). Genetic defect may confer resistance to certain viral infections. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2014/04/140409204511.htm
NIH/National Institute of Allergy and Infectious Diseases. "Genetic defect may confer resistance to certain viral infections." ScienceDaily. www.sciencedaily.com/releases/2014/04/140409204511.htm (accessed July 29, 2014).

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