Surprising Complexity of Virus/Host Cell Interactions - Article Example

Name: Course: Tutor: Date: The Surprising Complexity of Virus/Host Cell Interactions Revealed by the Powerful Systems Biology Approaches of Genomics and Proteomics “Viruses make hefty genetic commitments in order to tinker with their hosts’ systems” (Fields et al, 2006. p169). This statement is all that describes the complexity of host cell interactions in response to viral infections. Viruses have been found to be unstable and evolve in order to survive in host cells. Fields et al (2006), in their virology book, note that viruses evolve and develop a variety of mechanisms through which they adapt, modify, recruit and usurp the cellular mechanisms of hosts that they infect. Viruses as it is known have no ability to neither survive on their own, nor manufacture their own energy; the organisms depend on host cell mechanisms even for their own replication and yet they end up controlling the cellular mechanism of the host cell. The reason to their ability to survive under different conditions is mutation and some regulatory mechanisms that they posses (Bastolla et al, 2007). The viruses mutate to suit the environments they live in, that is, they form genes which encode for proteins that will enable them survive. If for example a virus invades a cell and finds the cell has the capability of eliminating it from the host, it will mutate its genes to produce proteins that are unrecognizable to the immune system of the host so that they remain in the host’s cell unrecognized (Bastolla et al, 2007). Fields and his colleagues also indicate that a large fraction of the viral genome encodes regulatory molecules of many kinds due to the evolutionary niche that the viruses have been found to belong. This is after the requirements for the structural virion are met. This gives the viruses the ability to evolve and live in many different conditions by manipulating host systems using the regulatory molecules that the viruses encode for (Fields et al, 2006). The complexity of the virus–host cell interactions due to the genetic commitments of the virus is all that this paper aims to describe. The role of genomics and proteomics in revealing these interactions will also be described. A general description is given with a few specific examples. The Complexity of Virus Host Cell Interactions The reason why the host cell interactions are considered complex is because of the diverse strategies that viruses have in ensuring survival. There are six principles of virus- host cell interactions (that is, the six basic tasks that viruses accomplish to ensure survival). These are; a) It has to enter the cell and translocate its genome to the replication site. b) It must replicate and produce mRNA. c) It has to produce viral proteins. d) It must assemble the viral progeny that will then be released to infect other cells. e) It has to escape from the host’s defense system. f) It has to disperse and persist in the host environment (Fields et al, 2006). The outcome of the response to infection is therefore dependent on the interactions involving the expression of genes and proteins of the host cells and the virus (Zhou et al, 2004). Hosts have a defense system that recognizes foreign or harmful organisms and eliminates or kills them, but when an organism has a way of escaping from the immune system, the response of the host cell also changes. The complexity is in the different strategies that the virus uses to; enter the host cell, replicate, and escape from the defense system of the host. Viruses enter the host cell through so many systems irrespective of the defenses of the host. This is determined by the genes that encode protein receptors which enable entry into the host (Rapley and Harbron, 2004). Generally, viruses have genes that encode for how to escape from the host defenses so that they remain in the environment either in the latent state, persistent state and form chronic diseases, acute diseases or cause cell death or host death. All these lead to different virus-host interactions which are classified into seven categories. These include; acute, persistent, slowly progressive, chronic, inapparent, tumorigenic and latent infections (Dimmock and Primrose, 1994). EBV for example produces different responses based on the type of infected cells, the environment and the response of the host’s immune system cells. According to Yefenof (2008), the emergence of EBV induced malignancies is dependent on the infected cells of the immune system and the response of the immune system to infection. EBV infects different cells of the immune system. It infects the B-lymphocytes, the epithelial T- and NK lymphocytes (Yefenof, 2008). EBV has a high degree of B-cell tropism and binds to a specific surface molecule of the B-lymphocyte CD 21. If EBV infects the B-lymphocyte cells, after the binding of the viral envelop to the B-cell surface receptor, cell activation is induced. The cells enter a mitotic cycle and continue to proliferate. The viral genome is maintained in an episomal state and expresses nine proteins. This prompts a response from the host cell and phenotypic changes are observed. One of the responses is the expression of co-stimulatory cell surface molecules that can be easily recognized by the immune system, therefore elimination. When this happens, no EBV induced malignancies emerge (Yefenof, 2008). Viruses are said to live by coping in order to survive. The micro-organisms have to ensure their hosts live in order to live as well. In some cases however, the responses by the hosts and the effects of the viral activities lead to host death. It has been found that EBV maintains a harmless state in humans by the modulation of its gene expression without causing immunogenicity. The host response also ensures the maintenance of the harmless condition by exposing the growth promoting EBV encoded proteins, that are recognized by the immune system hence eliminated (Yefenof, 2008). EBV causes latent infection in B-cells and produces infectious mononucleosis in some individuals which shows a response of the immune system that differs in severity and symptoms. When EBV infects the NK lymphocytes and the epithelial T cells, the response is different and malignancies associated with EBV only occur when there are additional factors that induce proliferation. In B- cell lymphomas however, proliferation is induced autonomously (Yefenof, 2008). Already this virus has shown different strategies of infecting the host cell. It can infect the T cells, the B-cells or the NK lymphocytes and still survive in the host. It however causes production of different responses by the host cell, yet it is one species of virus. In one of the principles of ensuring survival, the virus has to escape from the host defense system. This is a strategy that the viruses use to evade the host defense mechanisms. Hosts have so many defense mechanisms which prevent the virus from entering the host or from causing infection, but the virus has counter measures to the defense mechanisms (Mayer, 2008). These defense mechanisms include the skin, lack or membrane receptors for the virus, low PH, mucus in some cases, humoral components such as interferon, the complement system, antibodies and cytokines, and cellular components such as NK cells, T cells and macrophages (Mayer, 2008). Viruses must evade some of these mechanisms in order to propagate and live in the hosts. According to fields and others, viruses encode RNAs and proteins that interfere or interact with the cellular immune system hence evasion of the defenses (Fields et al, 2006). An example of evasion is in the interferon system. The induction of the interferon system when there is a viral infection happens when the system’s sensor (MDA5) binds to the dsRNA molecules that are produced in the course of infection. Some viruses produce V proteins that bind this cellular helicase hence preventing induction of the interferon system. When the normal defense system has been interfered with, the cell response will not be normal and the interaction will be altered as well. This is what leads to complex host interactions with different viruses (Fields et al, 2006). Another virus HPV 16, has been found to encode E6 protein that binds to interferon response factor three, thereby preventing RNA synthesis. IRF-3 is an important transcription factor in the interferon induction pathway (Fields et al, 2006). HIV is another virus which has been studied using genomic and proteomic approaches. The studies have revealed that HIV-I has HDF genes which are highly expressed in immune cells. The reason why these genes would be expressed so much is for the survival of the virus in the cells which it infects, that is, the immune cells. This virus also uses a karyopherin (TNPO3) to integrate, retrograde Golgi transport proteins (Rab6 and Vps53) to enter host cells and Mediator complex (Med28) for transcription (Brass et al, 2008). These are just examples of how viruses make the interaction with the host cell complex. Viruses have diverse strategies which are not all noted in this discussion, but these strategies make the host cell interaction with the virus very complex. The Role of Genomic and Proteomics Analysis of host pathogen interactions forms the basis of research nowadays and this has been made possible by genomics as Shaw indicates (2002). Host-pathogen interactions analysis has been made possible by the identification and completion of several microbial genome sequences (Shaw, 2002) and several genomic approaches have enabled the identification and characterization of virulence genes (World Health Organization). An example of a genomic approach is the microarray analysis which is used to indentify specific genes of organisms (Rapley and Harbron, 2004). The identification of the specific receptor of EBV and the host cell interactions to the virus have been made possible by in vivo visualization procedures of genomic medicine (Yefenof, 2008; Sanchez, 2004). Genomics enable proteomic analysis of pathogens. With complete sequences of certain genomes responsible for certain actions that enable the virus to survive in the host, encoded proteins can be identified therefore cell interactions and ways of treatment and development of vaccines determined (Engelbrecht et al, 2005). Protein to protein interactions and protein complexes can be identified by proteomics (Liebler, 2002). Proteomics enables identification of proteins therefore the ability to identify what proteins are encoded by the viruses when they invade the host or during host cell response to its invasion. Without genomics and proteomics, knowledge about the growth promoting proteins of EBV, the cells types that the EBV infects and the receptor that EBV uses to enter the host would not be known and the knowledge about how this virus is eliminated or made harmless is the body would not be understood (Yefenof, 2008). Cellular glycol-conjugates have been found to be important for viral and bacterial invasions of host organisms. Identification of these cellular glycol-conjugates is possible by approaches that identify and characterize the genomes and proteomes. One of the approaches is the glycomic studies of the infectious diseases that use the total carbohydrate complement to determine the structural diversity and selectivity of the host tissue expression, and viral components expressed during infection. Host cell interactions are therefore revealed by the structures identified since the antigenic structures and receptors used by the viruses, are composed of polysaccharides (Rapley and Harbron, 2004). Genomics and proteomics have therefore played an important role in science by revealing the virus-host cell interactions through different approaches which are important in therapeutic discoveries. References Bastolla, Ugo., Porto, Markus., Roman, H. E. and Vendruscolo, Michele., 2007, ‘Structural Approaches to Sequence Evolution: Molecules, Networks, Populations’, New York: Springer. Brass, Abraham L., Dykxhoorn, Derek M., Benita, Yair., Yan, Nan., Engelman, Alan., Xavier, Ramnik J., Lieberman, Judy., and Elledge, Stephen J., 2008, ‘Identification of Host Proteins Required for HIV Infection Through a Functional Genomic Screen’, Science Express. Vol: 319. no. 5865, pp. 921 – 926. Dimmock, N. J. and Primrose, S. B., 1994, ‘Introduction to Modern Virology’, Ed. 4, Oxford: Wiley Blackwell. Engelbrecht, Rolf, European Federation for Medical Informatics, Geissbuhler, A. and Lovis, C., 2005, ‘Connecting Medical Informatics and Bio-Informatics’. Proceedings of MIE2005 : the XIXth International Congress of the European Federation for Medical Informatics. Bernin, Germany: IOS Press. Fields, Bernard N., Knipe, David Mahan., Howley, Peter M. and Griffin, Diane E., 2006, ‘Fields' Virology: Viral Conquest of The Host Cell’, Ed. 5, London: Lippincott Williams & Wilkins. Liebler, Daniel C., 2002, ‘Introduction to proteomics: tools for the new biology’, New Jersey: Humana Press. Mayer, Gene., 2008, ‘Virology: Virus-Host Interactions’. Microbiology and Immunology Online. University of South Carolina. Retrieved on 11th May 2009 from: http://pathmicro.med.sc.edu/mayer/vir-host2000.htm Rapley, Ralph and Harbron, Stuart, 2004, ‘Molecular Analysis and Genome Discovery’ Queensland: John Wiley and Sons. Sanchez, Fernando, Martin, 2004, Informatics in Genomic Medicine. Pp.1-5 Retrieved on 11th May, 2009 from: ftp://ftp.cordis.europa.eu/pub/ist/docs/ictbio/ictbio-18a.pdf Shaw, Karen Joy., 2002, ‘Pathogen Genomics: Impact on Human Health’, New Jersey: Humana Press. World Health Organization. Advisory Committee on Health Research, World Health Organization, 2002, ‘Genomics and world health: report of the Advisory Committee on Health Research’, World Health Organization. Yefenof, Eitan., 2008, ‘Innate and Adaptive Immunity in the Tumor Microenvironment’, New York: Springer. Zhou, Jizhong., Thompson, Dorothea K., Ying Xu, and Tiedje, James M., 2004, ‘Microbial Functional Genomics’. New York: Wiley-IEEE. Read More

These are; a) It has to enter the cell and translocate its genome to the replication site. b) It must replicate and produce mRNA. c) It has to produce viral proteins. d) It must assemble the viral progeny that will then be released to infect other cells. e) It has to escape from the host’s defense system. f) It has to disperse and persist in the host environment (Fields et al, 2006). The outcome of the response to infection is therefore dependent on the interactions involving the expression of genes and proteins of the host cells and the virus (Zhou et al, 2004).

Hosts have a defense system that recognizes foreign or harmful organisms and eliminates or kills them, but when an organism has a way of escaping from the immune system, the response of the host cell also changes. The complexity is in the different strategies that the virus uses to; enter the host cell, replicate, and escape from the defense system of the host. Viruses enter the host cell through so many systems irrespective of the defenses of the host. This is determined by the genes that encode protein receptors which enable entry into the host (Rapley and Harbron, 2004).

Generally, viruses have genes that encode for how to escape from the host defenses so that they remain in the environment either in the latent state, persistent state and form chronic diseases, acute diseases or cause cell death or host death. All these lead to different virus-host interactions which are classified into seven categories. These include; acute, persistent, slowly progressive, chronic, inapparent, tumorigenic and latent infections (Dimmock and Primrose, 1994). EBV for example produces different responses based on the type of infected cells, the environment and the response of the host’s immune system cells.

According to Yefenof (2008), the emergence of EBV induced malignancies is dependent on the infected cells of the immune system and the response of the immune system to infection. EBV infects different cells of the immune system. It infects the B-lymphocytes, the epithelial T- and NK lymphocytes (Yefenof, 2008). EBV has a high degree of B-cell tropism and binds to a specific surface molecule of the B-lymphocyte CD 21. If EBV infects the B-lymphocyte cells, after the binding of the viral envelop to the B-cell surface receptor, cell activation is induced.

The cells enter a mitotic cycle and continue to proliferate. The viral genome is maintained in an episomal state and expresses nine proteins. This prompts a response from the host cell and phenotypic changes are observed. One of the responses is the expression of co-stimulatory cell surface molecules that can be easily recognized by the immune system, therefore elimination. When this happens, no EBV induced malignancies emerge (Yefenof, 2008). Viruses are said to live by coping in order to survive.

The micro-organisms have to ensure their hosts live in order to live as well. In some cases however, the responses by the hosts and the effects of the viral activities lead to host death. It has been found that EBV maintains a harmless state in humans by the modulation of its gene expression without causing immunogenicity. The host response also ensures the maintenance of the harmless condition by exposing the growth promoting EBV encoded proteins, that are recognized by the immune system hence eliminated (Yefenof, 2008).

EBV causes latent infection in B-cells and produces infectious mononucleosis in some individuals which shows a response of the immune system that differs in severity and symptoms. When EBV infects the NK lymphocytes and the epithelial T cells, the response is different and malignancies associated with EBV only occur when there are additional factors that induce proliferation. In B- cell lymphomas however, proliferation is induced autonomously (Yefenof, 2008). Already this virus has shown different strategies of infecting the host cell.

It can infect the T cells, the B-cells or the NK lymphocytes and still survive in the host.

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