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Retroviruses General comparisons of the retroviruses Morphologically, SIV, HIV, FIV, and BIV are consistent. They are all complex spherical to pleomorphic viruses (on the order of 100nm in diameter) that are composed of a viral envelope (after lysis of host cell), protein matrix, and nucleocapsid. The outermost layer, or the viral envelope, is composed of a phospholipid bilayer composed of cell markers and proteins from the host cells, and in HIV and SIV, glycoproteins from the virus’ protein matrix project out as well. The matrix underneath is made up of a viral protein, (p17 in HIV and SIV). At the core of the virus lies the nucleocapsid, which is made up of another viral protein, (p24, in HIV and SIV). The rod-shaped nucleocapsid harbors the two copies of the viruses genome in two positive ssRNA associated with a number of nucleocapsid proteins such as reverse transcriptase and integrase.Genetically, all four viruses are flanked by long terminal repeat (LTR) regions with the post-transcriptional modifications, presumably for preserving the RNA’s life, such as a 5’ G-methylated cap and a poly A tail. Moreover within their genomes, at least these three major genes are conserved: gag, pol and env, all of which are critical for formation of the virus. Gag is responsible for the number of proteins which are related to nucleocapsid and membrane anchoring. Pol codes for many of the nucleocapsid proteins, such as protease, reverse transcriptase, integrase, and RNase H. Env codes for important glycoproteins which bind to host cell receptors to allow for the invasion of the viral genome and proteins into the host. Pathologically, they all possess the ability to infect T cells and monocyte/macrophages via cell surface receptors. Engineering Applications/Modifications of Retroviruses In terms of bioengineering retroviruses, recently lentiviruses, such as SIV, HIV, SIV and BIV, have been considered has gene therapy vectors for non-dividing or slow-growing cells as well as prolific cells. Notably, lentiviruses have been used to induce pluripotency in human cells by viral transduction of Oct4, Sox2, Klf4, and c-Myc.Protein conservation between immunodeficiency viruses The gag protein, pol polypolyprotein, and envelope polyproteins appear to be highly conserved within the four immunodeficiency viruses. Below are multiple sequence alignments with conservation scores between the the gag, pol, and evelope proteins of BovineIV, FelineIV, HIV-1, HIV-2, and SimianIV. The multiple sequence alignments were generated using MAFFT and viewed in JalView. A tree is also contructed using a average distance method between the sequences. Please refer to individual sections of the viruses to browse their genomes and find information specific/pertinent to that individual virus.MSA and tree for the Gag polyprotein Multiple sequence alignment 
MSA and tree for the Pol polyprotein Multiple sequence alignment 
MSA and tree for the Env polyprotein Multiple sequence alignment 
From the analysis of these three proteins alone, we cannot conclude the evolutionary relationship between these four retroviruses. More genes must be brought in to make more reliable conclusions about the evolutionary relationship at the species level. Jenn Brophy (who is working on the annotation of Rhinovirus) suggests an evolutionary species tree in the context of more viruses. Her suggested tree can be accessed at: http://biowiki.org/view/Fall09/Fall09VirusPhylogeneticTree References Shibata, Riri and Adachi, Akio.SIV/HIV Recombinants and Their Use in Studying Biological Properties. AIDS Research and Human Retroviruses. Vol. 8, Number 3, 1992. Mary Ann Liebert, Inc., Publishers.Center, J. Rob et al. Promoting Trimerization of Soluble Human Immunodeficiency Virus Type 1 (HIV-1) Env through the Use of HIV-1/Simian Immunodeficiency Virus Chimeras. Pluta, Krzysztof and Kacprzak, Magdalena M. Use of HIV as a gene transfer vector. Acta Biochimica Polonica: Vol. 56, No.4/2009, 1-000 Vannucci, Laura et al. Feline immunodeficiency virus vector as a tool for preventative strategies against human breast cancer. VETIMM-81813. 2009 Lin, L. H. et al. Feline Immunodeficiency Virus as a Gene transfer vector in the Rat Nucleus Tractus Solitarii. Cellular and Molecular Neurobiology: Springer Netherlands 1573-6830; 2009. Barraza, A. Romain. Human gene therapy vectors derived from feline lentiviruses. VETIMM. Vol. 123, Iss. 1-2, May 2008. St-Louis, Marie-Claude et al. The molecular biology of bovine immunodeficiency virus: a comparison with other lentiviruses. Animal Health Research Reviews(2004), 5:125-143 Cambridge University Press |
