Did you know...

 

Infant with RSV bronchiolitis showing how the bronchiolar lumen has been obstructed (*) with lymphocytic infiltrates and sloughed necrotic material3

 

…research performed in the Center for Lung Biology here at the University of South Alabama may lead to the world’s first treatment for respiratory syncytial virus (RSV), a leading cause of acute respiratory infection and hospitalization in young children?

RSV was first identified in 1956 as the pathogen inducing coryza in chimpanzees and subsequently linked to human respiratory disease [1, 2].  Although RSV infections cause symptoms similar to a cold, some patients with existing complications, such as low birth weight or chronic respiratory illness, progress to develop a life-threatening illness [3]. Currently, there are no effective treatment modalities [3] - a situation that may be changing.

RSV first invades the nasopharyngeal epithelium creating a multinucleated syncytium [3]. Following viral attachment, the virally encoded fusion (F) protein mediates fusion with the host cell. Once infected, the host cell synthesizes F protein, which localizes to the plasma membrane initiating fusion of adjacent epithelial cells, which forms the syncytium [4].  By these means, the virus spreads between cells yet evades host immune responses. The syncytium is eventually lysed, causing epithelial sloughing and necrosis as well as releasing more viral particles poised to infect new areas.  If a patient does not resolve the nasopharyngeal infection, then RSV can spread to the lower respiratory tract, where it causes bronchiolitis and pneumonia often resulting in hospitalization.  Recent reports suggest one of the long-term outcomes of severe RSV infection is an increased incidence of asthma and wheezing [3].  Treatment for acute RSV infection have limited efficacy.  Currently, a prophylactic therapy, palivizumab, using monoclonal antibodies to the F protein is the only strategy that has demonstrated consistent efficacy in reducing RSV hospitalizations in high-risk children [5]. Although effective, this preventative treatment is expensive and must be repeatedly administered, restricting its use to high-risk patients.   Further, patients can be repeatedly re-infected with RSV because durable immunity does not develop following infection.  Indeed, this inability to develop durable immunity and the lack of an effective vaccine means that RSV continues to be a major pathogen even in adults.

Paradoxically, early vaccine formulations worsened pulmonary disease in infants, and so 50 years after the discovery of RSV as a human pathogen, we still have no effective vaccine or treatment.  This need for an effective inexpensive therapy may well be met by a new treatment modality developed in the laboratory of Dr. Sailen Barik here at the University of South Alabama.  This new approach to RSV treatment is currently in Phase II clinical trials and is based on the intranasal delivery of short interfering RNA (siRNA) molecules.  These siRNA molecules are designed to specifically inhibit the translation of viral proteins, such as the F protein and holds great promise as an affordable therapy effective as either a vaccine against or a therapy during RSV infection.

References:

  1. Blount RE, Jr., Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956;92(3):544-549.
  2. Chanock R, Roizman B, Myers R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg. 1957;66(3):281-290.
  3. Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med. 2001;344(25):1917-1928.
  4. Thorburn K, Hart CA. Think outside the box: extrapulmonary manifestations of severe respiratory syncytial virus infection. Crit Care. 2006;10(4):159.
  5. Ogra PL. From chimpanzee coryza to palivizumab: changing times for respiratory syncytial virus. Pediatr Infect Dis J. 2000;19(8):774-779; discussion 811-773.

Author: Joel Andrews, B.S.
Chief Editor: Sarah Sayner, Ph.D., Oct. 2009.

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