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PROFILE.
 This blog is proudly run by two girls : - Nur Rashilah & - Tan Him Gee of MB0801, Nanyang Polytechnic ; School of Chemical & Life Sciences :) CONTENTS. - Formal Welcome - First Scoop To Virology - Viral Replication Strategies - Viral Replication Animation - Viral Genetics - Viroids & Prions - Virusoids - Baltimore Classification CREDITS. linkone linktwo Layout: hearteditorials Codes: -ambulance Icon: biconcave |
Viral Replication Strategies.
Moving on from the introduction on the previous post, we will now look into the replication strategies of viruses. First up, here's a run through of the stages involved in the replication of viruses: 1) Attachment 2) Penetration 3) Uncoating 4) Replication 5) Assembly 6) Release 1. Attachment Attachment to the cell surface is the first step in the infection of a cell. This is done through ionic interactions which are temperature-independent. Specific receptors like protein, carbohydrate or lipid on the outside of the cell are recognized by the viral attachment. Therefore, the cells whereby the receptors are not appropriate will not be susceptible to the virus. 2. Penetration The nature of virus will decide the way in which it enters a cell. Enveloped viruses (A) Entry by fusing with the plasma membrane. Some enveloped viruses fuse directly with the plasma  membrane, resulting in the internal parts of the virion to be immediately delivered to the cytoplasm of the cell. (figure 1).
(B) Entry via endosomes at the cell surface (figure 2)
http://pathmicro.med.sc.edu/mhunt/rep2.jpg Some enveloped viruses cannot fuse directly with the plasma membrane and require an acid pH for fusion to take place. These viruses are taken up by invagination of the membrane into endosomes. As the endosomes acidified, the latent fusion activity of the virus proteins is activated by a reduction in pH and the virion membrane fuses with the endosome membrane. This results in delivery of the internal parts of the virus to the cytoplasm of the cell. In poxviruses, the disruption of virus is induced by the host factors. The release of DNA from the core depends on viral factors made after entry. Orthomyxoviruses, paramyxoviruses and picornaviruses all lose the protective envelope or capsid upon entering the cytoplasm. An envelope viral protein in the influenza virus, called M2, may allow endosomal protons into the virion particle. This then results in its partial dissolution and permitting replication. M2 is a polypeptide of 97aa and it forms a tetrameric channel forming structure within the viral envelope. Amantadine and rimantidine are anti-influenza drugs which function in part by inhibiting M2. In cells treated with rimantidine, the nucleocapsid remains associated with matrix protein and does not go to the nucleus.
In retroviruses, the matrix protein probably stays associated with cytoplasmic membrane after entry. Reverse transcription ie copying the RNA genome into a double stranded DNA form is thought to take place in a structured remnant of the capsid in the cytoplasm. The enzyme concerned is reverse transcriptase. It is both an RNA and DNA directed DNA polymerase. It also has an associated RNAse activity. The process is illustrated below: It results in the formation of a double-stranded proviral DNA which is longer than the viral RNA by one copy of U3, R and U5. In reality, the procedure is more complicated than shown. There are probably more than 2 strand jumps because retroviral RNA is often broken or nicked. At every nick of necessity the RT complex has to switch to another RNA strand (remember that there are two present). The proviral DNA is transported to the nucleus and integrated into the cellular DNA. HIV is not thought to show any obvious preferences in the sites of integration. The viral enzyme catalyzing this process is called integrase. A linear form of the proviral DNA is integrated. This reaction is unique to retroviruses. Two bases are first removed from the linear DNA at the 3' end to give a 3' recess. A staggered cut 6 nucleotides apart is then made in the genomic DNA and the resulting 5' phosphates are ligated to the 3' OH groups. This leaves a gapped intermediate which is repaired. The reaction can take place in vitro in the absence of ATP. Cleavage always occurs at the same place in the LTR. The reaction does not go to completion in quiescent T cells. In herpesviruses, adenoviruses and polyomaviruses, the capsid is eventually routed along the cytoskeleton to nuclear envelope.
New virus particles are assembled. There may be a maturation step that follows the initial assembly process. 6. Release Virus may be released due to cell lysis, or, if enveloped, may bud from the cell. Budding viruses (figures 3 and 4) do not necessarily kill the cell. Thus, some budding viruses may be able to set up persistent infections. Not all released viral particles are infectious. The ratio of non-infectious to infectious particles varies with the virus and the growth conditions.
http://pathmicro.med.sc.edu/lecture/images/hiv_bud.jpg
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