Principles of Virology. Jane Flint

Чтение книги онлайн.

Читать онлайн книгу Principles of Virology - Jane Flint страница 118

Автор:
Жанр:
Серия:
Издательство:
Principles of Virology - Jane Flint

Скачать книгу

the pH of membrane fusion. Nature 371:37–43.

      Wilson IA, Skehel JJ, Wiley DC. 1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289: 366–373.

       These two seminal papers were the first to report the structure of a viral fusion protein, influenza HA. These studies established the foundation of models for the conformational changes occurring in viral proteins during fusion.

      Butan C, Filman DJ, Hogle JM. 2014. Cryo-electron microscopy reconstruction shows poliovirus 135S particles poised for membrane interaction and RNA release. J Virol 88:1758–1770.

       This study shows the structural changes occurring in the poliovirus capsid shell during entry.

      Carette JE, Raaben M, Wong AC, Herbert AS, Obernosterer G, Mulherkar N, Kuehne AI, Kranzusch PJ, Griffin AM, Ruthel G, Dal Cin P, Dye JM, Whelan SP, Chandran K, Brummelkamp TR. 2011. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477:340–343.

       This paper first identified the receptor for ebolavirus.

      Conley MJ, McElwee M, Azmi L, Gabrielsen M, Byron O, Goodfellow IG, Bhella D. 2019. Calicivirus VP2 forms a portal-like assembly following receptor engagement. Nature 565:377–381.

       This paper shows the formation of a pore in the capsid shell of caliciviruses that would allow the delivery of the (+) strand RNA genome to the cytoplasm.

      Harutyunyan S, Kumar M, Sedivy A, Subirats X, Kowalski H, Köhler G, Blaas D. 2013. Viral uncoating is directional: exit of the genomic RNA in a common cold virus starts with the poly-(A) tail at the 3′-end. PloS Pathog 9:e1003270.

       This study challenged the idea that the viral RNA 5′ end is first to exit the capsid during entry of all picornaviruses.

      Kane M, Rebensburg SV, Takata MA, Zang TM, Tamashita M, Kvaratskhelia M, Bieniasz PD. 2018. Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2. Elife 7:e35738.

       This paper examines the intertwined role of nucleoporins in HIV-1 nuclear import.

      Liu J, Yu C, Gui JF, Pang DW, Zhang QY. 2018. Real-time dissecting the entry and intracellular dynamics of single reovirus particle. Front Microbiol 9:2797.

       This paper uses microscopy techniques to track the entry of individual reovirus particles into cells.

      Wec AZ, Nyakatura EK, Herbert AS, Howell KA, Holtsberg FW, Bakken RR, Mittler E, Christin JR, Shulenin S, Jangra RK, Bharrhan S,Kuehne AI, Bornholdt ZA, Flyak AI, Saphire EO, Crowe JE Jr, Aman MJ, Lai JR, Chandran K. 2016. A “Trojan horse” bispecific-antibody strategy for broad protection against ebolaviruses. Science 354:350–354.

       This study relies on the unique understanding of Ebolavirus entry to generate novel antibodies that inhibit entry by being delivered to the appropriate subcellular compartment.

      1 You are studying a new DNA virus. You have two cell lines: cell line α expresses the receptor (permissive) but is not susceptible (multiple blocks to the viral reproduction cycle) and cell line β is not permissive but is susceptible. Which of the following statements are correct and why?Transfection of the virus DNA into α will lead to production of infectious particles.Transfection of virus DNA into β will produce infectious particles.Inhibiting production of the receptor in α will allow virus reproduction.Production of the virus receptor in β will allow virus reproduction.

      2 You are working on a rhabdovirus that is cytopathic in dog cells but not rodent cells. What strategy would you use to identify the receptor in each cell line?

      3 The S (spike) glycoprotein of coronaviruses can engage receptors by the N-terminal domain, the C-terminal domain, or both. The C-terminal domains of both human SARS coronaviruses bind ACE2 (angiotensin-converting enzyme 2) whereas that of MERS-CoV binds DDP4 (dipeptidyl peptidase 4). In contrast, in mouse hepatitis coronavirus (MHV) the N-terminal domain of S binds CEACAM (cell adhesion molecule 1). You have identified a novel coronavirus with an S protein that displays similarity to MHV at the N terminus and to SARS at the C terminus. What are the molecules most likely to function as receptors and how will you test this?

      4 Viral fusion proteins mediate fusion between the viral and cellular membranes. This process begins with the insertion of fusion peptides or loops into the target cellular membrane; however, this step alone is not sufficient to complete the fusion process. Describe how additional conformational changes drive fusion.

      5 Which of the following statements is correct?Non-enveloped virus entry does not depend on binding to a receptor.For enveloped viruses with multiple envelope proteins on their surface, all envelope proteins engage cell surface receptors.Viral fusion proteins on the surface of enveloped viruses cannot engage a receptor.Fusion of enveloped viruses can occur at the plasma membrane or at compartments of the endosomal pathway.

      6 What experiments would you perform to determine whether endosome acidification is required for entry by a particular virus?

      7 You produce a viral fusion protein in cells and cocultivate them with cells expressing the receptor. Would you observe cell-to-cell fusion? If you don’t observe this result, what are the possible explanations?

      8 Describe the ways in which viral and subviral particles can be transported inside the cell.

      9 What are the potential disadvantages for a virion reaching the lysosome?

      10 Which of the following pathways would achieve delivery of the viral genome to the nucleus?Delivery of the viral genome to the cytoplasmic side of the nuclear poreHaving a capsid smaller than 39 nmDocking of a partially uncoated capsid to the nuclear pore that does not result in further uncoating or transport through the poreInteraction of the capsid with components of the nuclear pore that leads to subsequent transport and uncoating in the nucleus

      11 For retroviruses that rely on cell division to access the host chromatin, how does the viral genome remain in the nucleus once cell division is completed?

image

        Introduction

        The Nature of the RNA Template Secondary Structures in Viral RNA Naked or Nucleocapsid RNA

        The RNA Synthesis Machinery

Скачать книгу