Genome delivery and ion channel properties are altered in VP4 mutants of poliovirus.

نویسندگان

  • Pranav Danthi
  • Magdalena Tosteson
  • Qi-Han Li
  • Marie Chow
چکیده

During entry into host cells, poliovirus undergoes a receptor-mediated conformational transition to form 135S particles with irreversible exposure of VP4 capsid sequences and VP1 N termini. To understand the role of VP4 during virus entry, the fate of VP4 during infection by site-specific mutants at threonine-28 of VP4 (4028T) was compared with that of the parental Mahoney type 1 virus. Three virus mutants were studied: the entry-defective, nonviable mutant 4028T.G and the viable mutants 4028T.S and 4028T.V, in which residue threonine-28 was changed to glycine, serine, and valine, respectively. We show that mutant and wild-type (WT) VP4 proteins are localized to cellular membranes after the 135S conformational transition. Both WT and viable 4028T mutant particles interact with lipid bilayers to form ion channels, whereas the entry-defective 4028T.G particles do not. In addition, the electrical properties of the channels induced by the mutant viruses are different from each other and from those of WT Mahoney and Sabin type 3 viruses. Finally, uncoating and/or cytoplasmic delivery of the viral genome is altered in the 4028T mutants: the 4028T.G lethal mutant does not release its genome into the cytoplasm, and genome delivery is slower during infection by mutant 4028T.V 135S particles than by mutant 4028T.S or WT 135S particles. The distinctive electrical characteristics of the different 4028T mutant channels indicate that VP4 sequences might form part of the channel structure. The different entry phenotypes of these VP4 mutants suggest that the ion channels may be related to VP4's role during genome uncoating and/or delivery.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Capsid Protein VP4 of Human Rhinovirus Induces Membrane Permeability by the Formation of a Size-Selective Multimeric Pore

Non-enveloped viruses must deliver their viral genome across a cell membrane without the advantage of membrane fusion. The mechanisms used to achieve this remain poorly understood. Human rhinovirus, a frequent cause of the common cold, is a non-enveloped virus of the picornavirus family, which includes other significant pathogens such as poliovirus and foot-and-mouth disease virus. During picor...

متن کامل

Towards new structural insights into the process of Poliovirus RNA translocation upon infection

Poliovirus is not only a significant human pathogen but also serves as a well-characterized model system for understanding how nonenveloped viruses infect cells. Upon binding to its receptor at the membrane of human macrophages, Poliovirus undergoes an irreversible conformational change that leads to penetration of the host cell membrane. Thereafter, it translocates its single stranded RNA geno...

متن کامل

Simulation study of the transport properties of ions through ion channels serving as primary components of a nanobiosensor

Ion channels are naturally occurring pores through the proteins that regulate the passage of ions and thus maintain the concentration of ions inside and outside the cell. The ion channels control many physiological functions and they can show selectivity for a specific ion. Ion channels are mostly observed in nerve cells and muscle cells. The influx of ions into cells can be regulated by a gate...

متن کامل

Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine.

To identify determinants of attenuation in the poliovirus type 1 Sabin vaccine strain, a series of recombinant viruses were constructed by using infectious cDNA clones of the virulent type 1 poliovirus P1/Mahoney and the attenuated type 1 vaccine strain P1/Sabin. Intracerebral inoculation of these viruses into transgenic mice which express the human receptor for poliovirus identified regions of...

متن کامل

Simulation study of the transport properties of ions through ion channels serving as primary components of a nanobiosensor

Ion channels are naturally occurring pores through the proteins that regulate the passage of ions and thus maintain the concentration of ions inside and outside the cell. The ion channels control many physiological functions and they can show selectivity for a specific ion. Ion channels are mostly observed in nerve cells and muscle cells. The influx of ions into cells can be regulated by a gate...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of virology

دوره 77 9  شماره 

صفحات  -

تاریخ انتشار 2003