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Unformatted text preview: 9/27/11 1 Virus Structure • Nucleocapsid – Nucleic Acid – Capsid • Additional surrounding viral proteins • host cell membrane Viruses (not alive) • May have envelope (HIV does) • Viral protein spikes (HIV does) • Outer protein capsid (HIV does) • DNA-based genetics (HIV does not) or • RNA-based genetics (HIV does) – Retroviruses (Reverse Transcription) Models for studying severe immune defects • Retroviral diseases in other animal models • Immune disorders in humans • Combination of animal models and human immune disorders Retroviruses • Transforming cancer • Cytopathic destroys cells • HIV both? Lentiviruses (Slow Viruses) One Branch includes HIV-1 HIV-2 SIV HIV Structural Genes and Proteins • pol gene – Generates three enzymes • RT • PR • IN • gag gene – Nucleocapsid proteins (CA - p24) - surrounds RNA – Matrix proteins (MA - p17) – interior to envelope • env gene – gp160 • gp120 and gp41 9/27/11 2 HIV-1 auxiliary/non-structural proteins • Six genes with multiple functions • vif, vpr, tat, rev, nef, vpu – Role in completing viral lifecycle • Localizing viral DNA to nucleus • Activating full-length transcription • Exporting viral transcripts • Packaging/assembly of virion • Protection HIV from host cell attack – Affects cells infected with HIV • Makes cells “permissive” for infection • Alters cells to increase viral lifecycle – Also can make lethal proteins to uninfected cells Genetic Comparison between HIV 1 and HIV 2 • Share same structural genes – gag, pol, env • Share most of non-structural genes – vpu vs vpx is exception • Organization of genomes are different • Actual nucleotide sequence of genes are different HIV infection and replication • HIV-1 infection of cells occurs through specific protein interactions between the virus and the permissive host cell • Viral entry of cells • Release and copying of HIV genome • Integration of HIV genome into host chromosome • Expression of viral genes • Assembly of viral proteins and RNA • Release of virus HIV infection involves 3 main steps 1. Binding and attachment of virion to cell 2. Fusion of viral membrane with cell membrane 3. Entry of capsid and viral proteins into host cytoplasm These steps involve specific protein- protein interactions between virus and cell • Viral Entry Requires Specific Cell Receptors to HIV • Protein-protein interactions between virion and host cell required • Conformational changes occur due to interactions • Results in close interaction of virion and host cell membrane Viral Entry Requires Specific Cell Receptors to HIV • Viral spike (trimeric gp120/gp41) attaches to host cell surface proteins • gp120 binds to surface receptor of host cell – Highest affinity is to CD4 receptor • Binding results in gp120 conformational change • Altered gp120 binds to co-receptor...
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