Virus-host Receptor Interactions in Biology

Virus-host Receptor Interactions in Biology Abstract Viruses are obligate intracellular parasites and, as such, must penetrate a suitable host cell in order to replicate their genomes and disseminate. Most viruses are limited to a specific set of cells or tissues in which they can successfully replicate, and this may be in one or more particular species. When viruses are able to bind a variety of cells, the pathogenesis and overall effect on the organism may differ. The main determinants of viral tropism differ between different virus families, but in order to take the first, and arguably most important step, in the infection of a host cell, the virus must attach via specific interactions between cell surface molecules and viral proteins. Enveloped viruses usually have proteins embedded in their envelope, assembled at the host cell surface prior to budding. In the case of some viruses (such as HIV-1), these may even consist of cellular proteins from the host cell itself. Non- enveloped viruses are usually internalized in some way and uncoated in an endosome in a pH-dependant manner. Many viruses require a number of cell surface receptors for cell entry, and it is this combination, added to other factors such as replication proteins, that determine whether or not a virus can penetrate and replicated within a certain cell. Introduction As obligate intracellular parasites, the life cycle of viruses depends on an intracellular replication phase and they are thus dependant on living cells. The first essential interaction a virus makes with a host cell is with a cell-surface receptor. A viral receptor may be defined as any cell surface component that mediates recognition of a cell and facilitates entry of the virus and subsequent infection. Receptors serve to ensure infection by overcoming repulsion between the virus and cell. (Baranowski, Flint, Jindrak, modern virol) Cellular receptors are generally proteins, although other types of receptor, such as carbohydrates, may be used (see table 1). These molecules are essential components of the cell or extracellular matrix and functions may include cell adhesion, signalling e.g. chemokine and growth factor receptors. (Baranowski 2003) While some viruses require only one receptor, binding to one cellular receptor alone may not be sufficient for initiation of infection for other viruses. Viruses may bind two or more receptors in sequence in order to initiate endocytosis or membrane fusion. For some viruses, the first contact with a cell is through a low-affinity interaction with a ubiquitous molecule, which allows the primary receptor-virus interaction to take place. The primary receptor is generally unique to certain cells and therefore partly defines the tropism of that particular virus, as cells are rendered susceptible to infection by a certain virus if the receptor required for attachment and entry is present. The primary attachment receptor may induce a conformational change in the viral envelope protein bound, to induce further interaction with the cell. (Modern Virology) A further interaction may then be required to initiate infection, performed by a coreceptor.The definition of the term coreceptor may sometimes be ambiguous, but generally, it is taken to be the molecule that induces fusion or penetration of a cell. This may be a further determinant of tropism, for example the interaction of HIV-1 Virus entry into a cell is the first step in the life0cycle of a virus; various mechanisms of viral cell enrty are shown in figure 1. The mechanism of entry varies between viruses, but all begin with the binding of a cellular receptor by a viral protein. Binding of a cellular receptor may induce endocytosis or formation of an endosome, the acidic environment of which induces uncoating; this may be dependent upon cellular proteins clathrin or caveolin. Enveloped viruses may require an acidic environment that will induce conformational changes in envelope proteins required to induce membrane fusion, while others, including the measles and HIV viruses, can fuse directly with the plasma membrane at neutral pH. (Baranowski) Fusion at the plasma membrane releases the nucelocapsid into the cytoplasm, where the virus can make its way to the nucleus or begin replication in the cytoplasm. The differences in these entry pathways are due to the nature of the molecular interactions between the vi ral components and target-cell receptors, for example, viruses that mimic the natural ligand of receptors for signalling molecules interefere with their signalling to promote viral entry into the cell and spread of infection. (Bomsell) Conformational changes resulting from the binding of a primary receptor that allow the binding of a fusion receptor are a common mechanism among various types of virus, including influenza and HIV type 1, examples and brief description. Similar to Influenza . Multiple receptors could be coreceptors and act together either to modulate each other or to contribute complementary functions. Alternatively, the receptors might act sequentially. Binding of the virus to the first receptor could cause changes in the virus or host that are necessary before the second receptor can bind (50). For those viruses in fluids with flow, such as blood or respiratory secretions, the initial binding must be able to effect rapid docking of the virus to its host cell. (Haywood) As previously stated, some viruses recognise more than one cellular receptor. The same receptor may also be used by more than one type of virus. (see table 1) Often, these are highly abundant in many tissues, for example, heparan sulfate can serve as a receptor for many viruses, including Human immunodefiecieny virus, Hepatitis C and Dengue Virus and as a co-receptor for Herpesviruses (excluding EBV). (ODonnel) CAR, acts as a receptor for both coxsackie and adenoviruses. (Schneider) Table 1 illustrates the diversity of cell surface molecules which viruses have adapted to recognise. Some viruses use more than one type of molecule as a primary receptor e.g. reoviruses bind to the beta-adrenergic receptor as well as NAN. (Flint) While the presence of certain receptors on host cells is vital to initiate infection, these interactions are not always sufficient to explain all aspects of cell, tissue and species tropism. (Flint)(Haywood, Schneider) Binding of a viral protein to a cell surface receptor does not necessarily mean a productive infection will follow, since a co-receptor may be absent or functional domains of the receptor may be blocked. (Baranowski) Absence of specific cytoplasmic or nuclear molecules may hinder the replication of some viruses, despite their permissivity. However, even a non-productive infection may induce pathogenic effects, for example, binding to specific receptor may induce the secretion of cytokines. (Schneider) A virus generally cannot infect a cell successfully in the absence of its specific receptor, so the distribution around the body of the receptor will act as a restriction on the range of tissues that can be infected and hence on the number of systems in the body where sig ns and symptoms of infection might be experienced. (Flint) In the true sense of the word, Tropism refers to the specific cells a particular virus is able to replicate in, although the use of receptor by a virus is increasingly a valid definition in the field of virology. Additional factors the cause viral tropism will not be considered in the context of this essay, although they may be mentioned briefly where relevant, since the focus of this review is the link between specific receptor usage and virus tropism and pathogenesis. (Kuhmann) The primary topics explored here are the virus-receptor interactions with cells that allow viruses to enter cells and initiate infection and how this relates to the tropism of the virus at a cellular and organismal level. I am to demonstrate how viral attachment and entry is often a complicated multi-step process, sometimes requiring many different cell and virus molecules. The viruses largely used to illustrate these points, Human Immunodeficiency Virus type 1 (HIV-1), Influenza A and Herpes Simplex Virus type 1 (HSV-1) are human viruses of medical significance, but the tropism of these particular viruses in other animals, along with other viruses specific to other animals will be discussed where relevant. The structure and genomic organisation of these viruses is irrelevant and is only discussed where it relates to the glycoproteins that interact with cellular receptors. Viruses of plants, fungi and bacteria are not discussed The presence on the cell surface of a protein that has been identified as the receptor for a given virus may not be sufficient for a productive viral infection, and there may be multiple mechanisms behind such restrictions: functional domains of the receptor may be blocked in some cellular context, additional proteins (or other cofactors) may be needed, or cells may exhibit impediments for completion of the infection cycle, despite an initial successful interaction with a functional receptor. HSV- Demonstrates how viruses may use a large number of viral proteins and receptors to bind and enter specific cells. (Hayashi and Yoon) and how the interactions are a complex multi-step process. Influenza multiple steps. binds many cell types Tropism is dependent on other receptors and interactions. Of the many examples, the interaction of  the human influenza A virus hemagglutinin  with N-acetylneuraminic acid, and the ensuing  conformational alterations involved  in pH-dependent membrane fusion, are one  of the best characterized at the structural  and functional levels (11) (Baranowski 2001)  example of proteolytic cleavage to aid spread and pathogenesis. Conformational change required for fusion HIV A well-documented case of use of multiple receptos is that of HIV-1 viruses and related viruses. Illustrates how a virus may use multiple coreceptors to mediate entry to different types of cells and thus influence the tropism of this virus. Uses some of the same receptors as other viruses (parallels between HIV, HSV and influenza) Multi-step process The interaction of the virion with the attachment receptor leads to the first conformational changes in the envelope proteins. This step enables the interaction with co-receptors, or entry mediators and further conformational changes at the plasma membrane. In enveloped viruses (top), this may deliver the energy for the direct fusion of the viral envelope and cellular membrane. Some enveloped and non-enveloped viruses require the low pH in acidic endosomes to induce this conformational change. Enveloped viruses may require the low pH to induce membrane fusion (centre). These mechanisms lead to the release and possibly uncoating of the virus genome, and the initiation of the virus replication cycle. Role of Viral Receptor Destruction While non-enveloped viruses typically undergo relase through cytolysis. Influenza and HIV-1 Viruses also demonstrate the importance of receptor-destroying activity on the infectivity of some viruses. This is imperative for the efficient release and cell-cell spread of the virus by preventing the glycoproteins on the newly-emerged virus from binding to the host cell receptors. It is also important for preventing superinfection of cells by the same or different viruses utilising the same receptor, which may result in cell death. The efficient budding and release of Influenza A virus from the host cell relies on the removal of Sialic Acid residues by Neuraminidase. In contract, the HIV-1 virus gp120 envelope glycoprotein downregulates the CD4 receptor after infection of monocytes, by stimulating TNF-ÃŽÂ ± production. Other cellular mechanisms contribute to down-modulation of CD4, including the gene product Nef, which causes CD4 internalisation respectively. The precursor of gp120 and gp41, gp160, has also been found to bind CD4 intracellularly in the presence of viral protein Vpu, resulting in retention of CD4 in the Endoplasmic Rectilium. Enveloped particles leave the infected cell inconspicuously  by budding and secretion. Nonenveloped viruses  are usually thought to undergo release through cell lysis,  but some may escape by secretory mechanisms after  budding into membrane bound compartments and then  losing their membrane (Altenburg et al., 1980). Others  may subvert cellular autophagy pathways to gain access  to exocytic organelles (Jackson et al., 2005).  (Marsh)

Issues in Multi Cultural Education

To date, only a handful of studies have empirically investigated the relationship between school locations and their constituencies. Taller. E. (2001). The students that are living in the low income areas of Richmond are more diverse than the ones that are living in the counties that surround the city. For instance, Houghton High School located in one of the low income areas of Richmond County has a Ninety Two Percent minority rate among there attending students. U. S. News and world report (2014).Fifty Six percent of the student population at Houghton High is economically disadvantaged. U. S. News and world report. (2014). Over half of the students that attend this high school receives free lunch. REV News. (2014). In 2013 while hosting the third annual white house science fair President Obama spoke on how one of his main focuses as president has been how to create an all-hands-on- deck approach to the STEM curriculum. The White House. (2014). This curriculum includes science, techn ology, engineering, and math. The White House. (2014).He also mentions how â€Å"We need to make this a priority to train an army of new teachers in these subject areas, and to make sure that all of us as a country are lifting up these subjects for the respect that they deserve. † The White House (2014). Right outside the Richmond County school district still located in Richmond State is Henries County. Located about 20 Minutes away from Houghton High is Deep Run High School which is part of the Henries County public school district.. Deep Run High School in contrast to Houghton High has a twenty percent minority rate.SKI 2 Guides (2014). The Majority of the students that attend Deep Run High School are white. KEY Guides (2014). Only about two percent of the students who attend this school participate in the free lunch program. KEY Guides (2014). These students also rank eighty nine percent in proficiency in math. U. S. News. (2014). The annual per pupil expenditure in Henrie s County Public Schools is 9,650 per pupil in 2013. Henries County Public Schools. (2014). The annual per pupil expenditure in Richmond County Public Schools is 11,218.Richmond County Public Schools. (2014). This proves that it the inequities do not lie in the shortage of money being provided by the local and federal funds. Individuals from families that are still together completed, on average, more years of school and are also more likely to graduate from high school, attend college, and complete college compared to students raised in blended or ingle-parent families. Family Facts (2014). Their parents have more involvement in their school activities and have higher expectations for them. Family Facts. 2014). The answer then to closing the gap on students' performance in school has to start with a program to inspire low income families to stay together and build a strong support system for one another to be successful. The Strengthening Families Program (SSP) is a nationally and i nternationally recognized parenting and family strengthening program for high-risk and regular families. Strengthening Families Program. (2014). This program teaches parents and students with broken home valuable skills that can increase their chances for success.It also has been shown to reduce problem behaviors, delinquency, and alcohol and drug abuse in children and to improve social competencies and school performance. Strengthening Families Program. (2014). Past research reported that teenage males from minority groups often engage more in high-risk behaviors at school such as weapon possession, gang involvement, and fighting than any other group. Marsh, T. Y. , & Cornell, D. G. (2001). The Strengthening families program's take home DVD had ten thirty minute sessions for parents and students to watch together.These DVD's can be viewed at the discretion of the family preferably once a week. The Strengthening Families Program is an excellent tool to use to help aid in situations where families are in low income single parent or poverty stricken situations. Grappling with the issues of equity and excellence has become ever more complex solutions seem more and more remote as the divides between socioeconomic groups become greater and greater, and ethnic diversity of the student population continues to present ever-increasing stress on the educational system. Callahan, C. M. (2003).Because of inequalities students that attend school in Henries, Chester field and surrounding counties are receiving a higher level of education than the students that attend school in certain parts of Richmond. Whether or not they are income based, minority based, or Just lack of good parenting. The fact still remains that there is a dish connect between students that are being raised in such a close proximity. How can people on one side of the tracks sit around and watch students on the other side of the tracts do so poorly in school? This problem is deeply rooted in the community as well as in the individual family unit.Through the implementation of people that care and some programs that could aid in recovery one day we will all be able to stand hand and hand and succeed as a whole.

Shakespeares use of the Renaissance Idea of Fatalism and...

Shakespeares use of the Renaissance Idea of Fatalism and Imagery in King Lear In a play about individual tragedies, fatalism plays an important part. Shakespeare effectively uses cosmic imagery to define his characters and to explore the idea of journeys linked to self-discovery by relating it to the imagery of rotating circles. Shakespeare uses Renaissance theology to explain character motivation. In the 16th century there was a great belief in astronomy. People believed in the harmony of the spheres and they were ruled by this idea of thhe natural alignment of the nine planets in their orbits. Shakespeare incorporates this into King Lear in highlighting Edgar and Gloucesters superstitious†¦show more content†¦Edmund turns away from the belief of the alignment of planets and harmonies and towards nature as that is all he can be really sure of. The fact that Edmund doesnt believe in spherical predominance proves that he is different to the society around him. Shakespeare takes every opportunity to emphasise this to distinguish evil from good in the play putting Edmund forward as a character who is out of harmony. When Gloucester predicts that eclipses in the sun and moon suggesting a bad omen, Edmund casts aspersions on this idea, accusing the world of foppery, describing it as excellent because he sees it as a weakness that he can exploit from his anti-human point of view. Edmund is also stating that people are fops or fools because they blame their evil and wrong doings, which is really part of their character our own behaviour, on the cosmos. Even though Edmund does rightly say that that when we are sick in fortune-often surfeits of our own behaviour-we make guilty of our disasters, the sun, the moon and the stars, as if we were villains on necessity, fools by heavenly compulsion (Act I.2.117-26) He declares that men are fools if they evade responsibility for their actions by blaming the stars He ultimately decides that man is what he is by choice, not by the stars and that he is evil. He appreciates no fate, only free will. He says that all cosmic followers

A Day in a Life a Summary of the Case and Some Questions

* Summary of the case This case shows a daily working life of Rachel, the project manager of a large information systems project, to mainly discuss whether she allocates her time appropriately or not. When we take a closer look at her works on that certain day, then we can classify those works into three parts: project related, non- project related, and routine works. After analyzing those works each by each, therefore we are able to get the concept easily of whether Rachel has been playing a good role in project manager. No matter the answer turns out to be yes or not, we still can improve her work schedule more efficient by viewing the result of our analysis. * Answers of the questions 1. How effectively do you think Rachel†¦show more content†¦So, from this point of view, there is no other job like project manager in terms of huge pressure. On the other hand, some people might think to be a project manager can feel a great deal of sense of achievement as long as finishing the task. Therefore, project manager is a job which needs all kinds of ability including organizing, allocating resources, communicating, cheering people, coordinating, politic skill, and so on. * Insights of the case A number of things I have learned from this case. First of all, Rachel, even though, spent 70% of her daily working time on dealing with project’s work directly, it doesn’t mean that she did effectively in the project itself. In other words, she still can save her time by taking care of client firm issue thoroughly and cautiously. Again, let’s take client firm’s case for instance. Regarding to the time table above, Rachel spent 130mins (25% of her total working time) just on handling this case! Is there any other way to prevent this kind of incident happened? Answer would be yes by having a great report system among each department’s head and Project manager, so that before things going to theShow MoreRelatedWhat Does Sequoyah s Life Story Tell You About Him And The Cherokee People? Essay995 Words   |  4 Pages1. What does Sequoyah’s life story tell you about him and the Cherokee people? The story of Sequoyah’s life demonstrates how the Cherokee people weren’t barbaric but they were fascinated in the white people’s technology. Some of the traits of the Cherokee people: Determination Proudness Open mindedness 2. Where were the Cherokee homelands and why did immigrants and others want those lands for themselves? 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