The Attachment and Penetration Methods of Different Viruses

Tasiya Sinclair A virus is essentially genetic information in the form of single or double stranded DNA or RNA. Although they possess a genome which can be used to replicate, their lack of metabolic systems as well as the biochemical machinery required to synthesise proteins result in them being entirely dependent on a host cell for reproduction and energy. Due to their need for a host they have adapted so that most organisms have a virus to which it can succumb. In order for a virus to become parasitic it must first invade its host cell during processes known as attachment and penetration. Viruses can only infect the host cells specific to them; as a result the first step in infection is to identify a suitable host. To do this viruses display proteins on their cell surface known as attachment receptors to which the proteins on the plasma membrane of the host cell can bind to. Once a suitable host has been found the virus then employs one of many mechanisms in order to gain access into the cell; this essay is concerned with those mechanisms. The use of Enzymes: The T4 bacteriophage Some viruses contain enzymes which penetrate the cell wall and membrane of their host cells allowing them to insert viral nucleic acid. One example of a virus which employs this mechanism is the T4 bacteriophage which infects Escherichia coli. Structure of T4 bacteriophage The structure of the T4 bacteriophage (Figure 1) consists of double stranded DNA enclosed in a icosahedron shaped capsid attached to a hollow tail. The tail is sheathed and attached to hexagonal base plate. Bonded to the base plate are tail pins and six kinked tail fibres. (Nancy Jo Trun, 2004) The Invasion of E. coli The bacteriophage gains access to the E. coli when the tail fibres interact with the polysaccharides on the gram negative envelope. They contract causing them to make contact with the cell wall, the bacteriophage then draws closer. A lysosome like enzyme is released, forming a hole in the peptiglycan. (Madigan, 2009)The molecular conformation of the base plate changes reducing its diameter and detaching from the tail core and allowing it to move up the core as the sheath retracts. The hollow tube within the centre of sheath enters the E. coli cell wall, viral nucleic acid is pushed out of the head and down the tube and into the bacterial cell near the protoplasmic membrane. (Simon, 1971) The DNA is then transcribed and translated resulting in the production of virons within the cell.

Figure 1 A T4 Bacteriophage Petr Leiman (Purdue University)

Figure 2 a) Tail fibres binding a lipopolysaccharide. b) Contact between tail pins and membrane c) Retraction of tail sheath so the viral DNA is allowed to pass into the cytoplasm (Madigan, 2009)

Viruses which do not have tails cannot utilise this method; however some animal viruses also require enzymes to penetrate their host albeit in a completely different way. One example is H5N1; the bird flu virus.

The Structure of Bird Flu The structure of the virus is similar to that of other influenza A viruses. It consists of a single negative strand of RNA which is segregated into eight pieces and enclosed in a protein capsid forming a helical nucleocapsid. (Madigan, 2009) It is enveloped in a membrane containing sialic acid and lined with a matrix protein. It has two antigenic glycoprotein enzymes present on its membrane; Hemagglutinin (HA) which is said to be rod shaped and neuraminidase (NA) which is said to be mushroom shaped. (S Padhi, 2004) Entry into the Cells of the Lower Respiratory Tract The virus is uncoated at the cell surface membrane; its HA binds to the sialosaccharides (-2,6-Galterminated saccharides) which are present on the cell surface membrane of the respiratory tract cells, for example alveolus macrophages, type II pneumocytes or the non ciliated epithelium. It also ensures that the virus only attaches to cells which contain sialic acid. NA is an enzyme Figure 4 which removes the sialic from glycoprotiens and glycolipids so that the viron is given access into the cell and to prevent it from disrupting the replication process. The virus is then taken into the cell by endocytosis. (Madigan, 2009; Hans-Dieter Klenk, 2008; S Padhi, 2004) Structure of HIV-1 HIV 1 is a retrovirus which comprises of two identical strands of RNA and RNA binding proteins (p7 and p9) enclosed by a capsid made up of the viral proteins p24 or p25. Surrounding the capsid is an envelope mad e up of p17 and a lipid bilayer which was made in the host cell. In turn the bilayer is enclosed in a glycoprotein coat consisting of spikes. (Jeremy Dale, 2004) The spikes are trimetric structures made from gp41 attached to gp120, both are glycoprotiens. (Subramaniam, 2006) Attachment and penetration of T Helper Cells The lipid bilayer and glycoprotein coat are host derived and as such can be used in the attachment and penetration of new host cells. The gp120 protein molecules on the coat interact with the CD4 receptors on the cell membrane of a T lymphocyte (which usually activates the cell in response to an infection). This occurs when the CD4 receptors bind to the gp120 due to the formation of hydrogen bonds and a salt bridge, causing the glycoprotein to significantly contract. As a result gaps are produced in the CD4 g120 complex, one is filled with phenylalanine and the other becomes occupied with water molecules. (Wyatt, 1998) The CD4 gp120 complex then interacts with a chemokine receptor protein. The complex can either bind to the CCR5 receptor or the CXR4 receptor. Which one is dependent on whether the HIV-1 is non-syncytium-inducing (M-tropic),

Figure 3 H5N1 virus (S Padhi, 2004)

Figure 5 HIV-1 ((NIAID))

Figure 6 Infection of a CD4 target cell with the human immunodeficiency virus (HIV). (1) gp120 protein on HIV binds with the CD4 receptor and the chemokine receptor (2) The envelope fuses with the cell surface receptor (3) Viral RNA and RNA transctiptase are deposited inside the cell.

or syncytium-inducing (T-tropic). (Kazmierski, 2005) Initially macrophages are infected and in those cases the virus is M-tropic and so the complex formed is CD4 gp120 CCR5. The virons produced from the infected macrophage have a glycoprotein coat produced with a different type of g120. When they infect T helper cells the complex they form is CD4 gp120 CXR4. (Madigan, 2009) The virus envelope then fuses with the plasma membrane of the host cell and the viral RNA and RNA transcriptase enter. Infected T cells may then display viral gp120 molecules on their cell surface membranes, the gp120 interacts with CD4 receptors on healthy T cells. The cells then fuse, one infected T cell can fuse with up to fifty healthy T cells to form large multinucleate cells called syncytia. (Madigan, 2009) Like HIV the Hepatitis C virus is an enveloped RNA virus but because of the physical differences between the cells they use to replicate they have entirely different methods of attachment and penetration. The Structure of Hepatitis C The Hepatitis C virus is a flavivirdae virus which has a positive sense strand of RNA which is joined to the capsid encapsulating it. The virus is enveloped in a heterodimer protein coat made up of E1 and E2 structural proteins. (Cheng, 2008) The Attachment and Penetration It is thought that Like influenza the virus enters by endocytosis. It exhibits pH dependant behaviour as at a certain pH the cell surface glycoprotiens refold allowing E2 to interact with the CD-81 and the SR-BI receptors on the cell surface membranes on the hepatocytes. Due to their completely different morphology plant cells are invaded in an entirely different way. One of the most studied of plant viruses is the Tobacco Mosaic virus, the following paragraphs will detail the structure of the plant pathogen and how it gets into its host cell. Structure of the Tobacco Mosaic Virus The tobacco mosaic virus is essentially a single strand of positive RNA wound around between rows of protein forming a rod shaped protein case. The capsid is made up of two thousand one hundred and thirty capsomers which are arranged in a helical configuration( see figure 7). (Reddy, 2001) Attachment and penetration does not occur in the case of the Tobacco Mosaic Virus because the cellulose cell walls of plants are strong and extremely resistant to pathogenic attack. Despite this it is an agricultural problem because it is so infectious. In order for the virus to enter the plant there must be damage, once inside uncoating takes place and the genome of the virus is transcribed and translated. Once a movement protein has been made it binds to the also newly synthesised viral RNA forming a thin complex which moves through the plasmodesmata and infects other cells
Figure 7 Tobacco mosaic virus (Madigan, 2009)

within the plant.

In conclusion the main point that can be taken from this essay is that viruses have developed a variety of ways in which to most successfully enter their host cell. They have adapted so they can successfully mimic other materials allowing them to interact with the receptors on the host membrane and gain entry. It is as if these viruses have been perfectly designed to be pathogenic to their particular host.

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