Poster Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Attachment factors, entry receptors and pathways for internalization of respiratory viruses (#178)

Patrick Reading 1 , Leah Gillespie 2 , Wy Ching Ng 2 , Sarah Londrigan 2 , Andrew Brooks 2
  1. WHO Collaborating Centre for Reference and Research on Influenza & Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  2. Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia

In addition to influenza A virus (IAV), members of the Paramyxoviridae family cause significant respiratory disease in humans. These include mumps virus (MuV), human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and parainfluenza viruses (PIV). It is well established that many paramyxoviruses use cell-surface glycans as attachment factors to concentrate virions at the cell surface, however little is known regarding the specific transmembrane receptors utilized by these viruses for infectious entry into host cells. For example, MuV and PIV utilize sialic acid (SIA) as an attachment factor whereas RSV and HMPV attach to the cell surface via glycosaminoglycans (GAGs). Recent studies from our group have defined interactions between IAV and calcium-dependent (C-type) lectins expressed by MΦ, DC and subsets of parenchymal cells. In particular, we have developed novel transfection/expression-based approaches to demonstrate that C-type lectin receptors (CLRs) can act as attachment and entry receptors for IAV infection in the absence of cell-surface SIA. Recently, we extended these approaches to investigate how human CLRs interact with paramyxoviruses in the presence and absence of cell-surface SIAs or GAGs. Of interest, glycans expressed on the surface glycoproteins of some paramyxoviruses can serve as ligands for CLR-mediated attachment and infectious entry into target cells. Moreover, while it is generally accepted that paramyxovirus entry occurs via direct fusion with the plasma membrane, we provide evidence that CLR-mediated recognition of some viruses, such as HMPV, results in endocytic entry and infection. Together, these studies define an experimental system to assess putative receptors for paramyxovirus attachment and entry. Furthermore, we demonstrate that in addition to fusion at the cell surface, alternative entry pathways can give rise to paramyxovirus entry and infection.