MicroBio 160 1st Edition Lecture 21 Outline of Last Lecture I Strange Diseases II AIDS III Does HIV cause AIDS IV Peter Duesberg and AIDS Dissidents V Koch s Postulate VI HIV 1 and HIV 2 VII Origins of HIV VIII How Did HIV Spread into Humans IX HIV Infection X What Lead to the Current HIV Epidemic Outline of Current Lecture I What are Viruses II Characteristics of HIV III Types of HIV IV V Major Viral Components HIV binding to CD4 T cell VI Replication of DNA VII HIV Integrase VIII HIV Protease IX HIV Pathogenesis X How does HIV destroy CD4 cells XI Syncytia Current Lecture What are viruses A virus particle or virion virus particle consists of the following Each individual shape are all different types of viruses o Nucleic acid Genetic instructions either single stranded or double stranded DNA or RNA These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute o Coat of protein Surrounds the DNA or RNA to protect it Accessory proteins are attachment proteins how a virus attaches to your cells o Lipid membrane Surrounds the protein coat of SOME virions stolen from host cell Called enveloped viruses Examples HIV and influenza No lipid membrane naked Characteristics of HIV An HIV particle is around 100 150 billionths of a meter in diameter That s about the same as o One seventieth of the diameter of a human CD4 white blood cell o 0 1 Microns o 4 millionths of an inch What type of virus is HIV HIV is a lentivirus slow all attack immune system o Found in a number of different animals including cats sheep horses and cattle Most interesting lentivirus is the Simian Immunodeficiency Virus SIV that affects monkeys so far unsuccessful but it is what we use as a model to study primates Generally accepted that HIV is a descendant of SIV because certain strains of SIVs bear a very close resemblance to HIV 1 and HIV 2 HIV 2 for example corresponds to SIVsm sm is the species it is found in a strain of the SIV found in the sooty mangabey also known as the green monkey indigenous to western Africa Major Viral Components structure Gp120 and Gp41 are two separate proteins that combine together Viral Envelope o P17 P24 Protease Reverse transcriptase RNA HIV binding to CD4 T cell Gp120 CD4 binding Conformation change which pulls the virus closer Gp120 CD4 BIND CCR5 cCXCR4 GP41 membrane penetration inserts itself into your membrane Membrane fusion Envelope virus when two plasma membranes meet together they fuse Replication of HIV 1 2 3 4 5 6 HIV attaches to host cell at membrane protein CD4 Viral envelope fuses with plasma membrane capsid breaks down and RNA is released Viral RNA uses reverse transcriptase to make complementary DNA cDNA Viral RNA degrades Reverse transcriptase synthesizes the second DNA strand cDNA enters the nucleus and is integrated into the host chromosome via HIV protein integrase forming a provirus it doesn t realize that it may be infected with HIV RNA polymerase doesn t know it isn t normal so it makes a copy of it 7 Upon activation proviral DNA is transcribed to viral RNA which is exported to the cytoplasm 8 In the cytoplasm the viral RNA is translated into proteins using host ribosomes RNA goes into the capsid proteins get inserted through the membrane the virus will butt off 9 Viral protein matures via HIV protease fully capable of infecting another cell 10 Viral glycoproteins new capsids RNA and viral envelopes are assembled 11 An assembled virus buds from the plasma membrane HIV Integrase HIV integrase is responsible for integrating HIV DNA into host cell DNA o It is an attractive target for anti HIV drugs On October 12 2007 the Food and Drug Administration U S approved the integrase inhibitor Raltegravir MK 0518 brand name Isentress TM The second integrase inhibitor elvitegravir was approved in the U S in August 2012 HIV Protease HIV PR cleaves newly synthesized polyproteins made by our proteins has to be cut up so we have infectious particles it can t spread to further cells to create the mature protein components of an infectious HIV virion Without active HIV PR HIV virions remain uninfectious Thus HIV PR inhibition is the subject of much research Protease inhibitors such as Atazanavir Lopinavir and Ritonavir are available for HIV therapy Why do they make good drug targets Because it is specific to HIV Cell Types Infected by HIV Innate immune system recognizes a pathogen and turns on a pathogen If it doesn t have CD 4 marker on the outside it can t infect it o Can also be CCR5 CXCR4 These cells have 3 receptors in common CD4 CCR5 and CXCR4 HIV uses these 3 receptors to enter hosts therefore HIV can infect all 4 of these cell types HIV Pathogenesis like to alert the body that there is an invader HIV infects your immune cells so it helps establish an infection inside of the lymphatic tissue due to the alert signal If you are infected with the virus your immune system has an immune response body responds to the HIV and starts killing it Your body has a hard time clearing HIV not easy to destroy immune cells not HPV o Destruction of the immune system occurs How does HIV destroy CD4 cells If hundreds of virus particles are living at the same time it cant survive Immune system cells take a piece of HIV and put it on the outside if the protein on the outside is gp120 then it is expressing the same thing o One cell infected with HIV and one that isn t fuse then they are both infect o As HIV comes in contact with new cells they become infected can happen to hundreds of cells o Nuclei begins to be knocked out Anytime a cell says their infected the cytotoxic t cells tell it to go through apoptosis HIV induced syncytia Syncytia can go into your brain and disrupt brain function
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