VPg protein structural evaluation - implications in replication and pathophysiology of human rhinovirus infection

• Grant number: 12/23304-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2013
• End date: May 31, 2015
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Nancy Cristina Junqueira Bellei
• Grantee: Nancy Cristina Junqueira Bellei
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Human rhinovirus (HRV) infections are the most frequent cause of common cold and are responsible for approximately 50% of all upper respiratory tract infections (URTI) described. Historically HRVs are associated to URTI, but with the development of diagnostic molecular techniques, the researches could demonstrate the association between HRV infection and lower respiratory tract infection. Recent studies have demonstrated that this virus is related with severe respiratory infections among children, adults, elderly and immunocompromised patients. Currently the HRVs are classified in to more than 140 serotypes, distributed in 3 distinct species: HRV-A, HRV-B and HRV-C, with A and C species clinically associated with onset of more severe disease. Several studies have demonstrated that host factors, as age, immune status and worse clinical outcome are not associated with one specific HRV species. A better understand of HRV molecular epidemiology raised new concerns about the mechanisms involved in pathogenesis of the different species. In this scenario the importance of viral physiology is evident. The HRV replication mechanism is initiated through a small genome binding protein called VPg (Viral Protein of the genome). The VPg acts as a primer for the negative intermediate strand, which will subsequently be transformed into a genomic positive RNA strand. Studies that show the VPg role in HRV replication described that mutations inserted in precursor gene of this protein (3B gene), result in defective RNA synthesis, demonstrating that this small protein plays an important role in HRV replication. Structural evaluation of VPg, and its role in the different species replication could clarify de infections dynamics and clinical diversity presented by subjects infected with the HRV different species. With data from structural and functional VPg conservation, the immunogenicity of this protein could be tested, as well as their use in diagnostic tests developing for HRV detection. (AU)