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Virology Week 4 Notes

by: Anastassia Erudaitius

Virology Week 4 Notes BIOL 123 001

Anastassia Erudaitius

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These notes cover what Dr. Rao discusses in lecture
Dr. Rao
Class Notes
UCR, Lecture, Virology, 123, BIOL
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This 10 page Class Notes was uploaded by Anastassia Erudaitius on Sunday April 24, 2016. The Class Notes belongs to BIOL 123 001 at University of California Riverside taught by Dr. Rao in Spring 2016. Since its upload, it has received 11 views. For similar materials see Virology in Biology at University of California Riverside.

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Date Created: 04/24/16
Virology Lecture 4/18/16  HIV has a very unique history compared to other viruses  History o Relatively new virus – discovered in 1980s o This virus was discovered in homosexuals o All of the patients were suffering from immune deficiency  Once your immune system is down you can get fungal infections, viral infections, and bacterial infections o 26 homosexual men had Sarcoma o 5 homosexual men had PCP o Because these diseases were exclusively associated with homosexuals the name GRIDS was given to the disease o Found other people contracting the disease  Hemophiliacs – blood cannot clot  IV drug users  All the children born to the IV drug users who had the disease, also had the disease  Evidence that HIV is not restricted to homosexuals o Initially thought the disease was blood-borne and sexually transmitted o 1982 – two types of groups working independently  one in U.S. the other in France o A lot of dispute over who first discovered the virus  The disease caused by HIV is AIDS o This is probably the only known case where the disease name is different from the virus o AIDS is not the virus it is the disease!  Determined that the virus existed in 1950 as well  The mean age of patients infected are 37  More males infected than females  Once a person develops AIDS many opportunistic infections result  All patients infected with HIV died 1 month to 6 years after the initial manifestation of the disease AIDS o Based on the first symptoms and when the person died  Many factors involved in how long a person infected with AIDS will live  Case of Robert R o Patient had intense welling of lymph nodes in neck o Very unusual symptoms o The virus didn’t initially exist in the human population  Blood transfusion is one of the means of getting HIV  Researchers found out that a similar virus existed in monkeys in Africa  SIV (Simian Immunodeficiency Virus) o The SIV virus however does not affect the monkeys o Another strain found in chimpanzees  A lot of research experiments done on mice and on monkeys  Did the simian virus infect humans? o Hypothesized that the virus did pass from primates to humans o Hunters of chimpanzees might cut themselves while preparing chimpanzee meat, and then became infected o Food would get contaminated as well (chimp head near bananas)  but the virus is not transmitted by eating!! Only by blood  so if you touched food with blood on it and had a cut or wound then you could get infected  Usually cooking the food kills viruses  We know that many viruses can cross species (originally not a human pathogen, came from animals to humans) o Anthrax o Bubonic plague o Avian flu o Mad-cow disease o SARS  Influenza infects more people (because of the way it spreads)  but immune system isn’t infected so you can fight the infection  HIV attacks your immune system  After discovering the virus in 1980 researchers discovered how the virus spread o Initially they thought it was spread through simple physical contact (shaking hands)  Immigrants are screened for HIV  Education has reduced the spread of the virus Virology Lecture 4/22/2016  The global position of the HIV crisis – 35.3 million people currently living with AIDS  Infections mainly come from Africa – lack of education, lack of sanitation  Major cause of HIV transmission is sexual contact o Next major cause is pregnancy and childbirth, and breastfeeding  Some of the viruses are found in the breastmilk o Next is injection drug use o Following that is occupational exposure o The least common way of transmitting the disease is blood transfusion  Most of the time blood transfusions are taken from family members o Most common form of HIV transmission from left to right (least common)  HIV doesn’t have any specific or unusual symptoms  symptoms often appear to be flu-like o Within 1 – 4 weeks of exposure, infected persons show flu-like symptoms  1/6 people could have HIV, because HIV doesn’t show symptoms you may not know you have HIV  1 in 4 people – infections in youth  You can see how the disease is distributed across the U.S. (2011)  Usually HIV infected people survive for 1 – 6 years after infection o Magic Johnson is an exception  HIV is NOT transmitted by insects  There are drugs to prevent exposure (PREP)  Some drugs help prevent after exposure (PEP)  One of the major sources of HIV contamination – adult film industry  Another major source of HIV contamination – correctional facilities  11%-17% of people living with HIV are 50+ years old  24-30% of men and women ages 60-74 report they are sexually active  Three phases of clinical symptoms o Within first 30 days HIV RNA is detectable , It takes almost a month to detect antibodies because the virus is not active soon after infection o Asymptomatic phase – the virus is in a really active state, but the person still does not show any symptoms of HIV – can last for 10 years o AIDS stage – patient will die within 2-3 years without treatment  The lymphocyte counts decrease to 50cells/microliter  At this point opportunistic infections result  Wasting syndrome – person will start drastically losing weight  The person is susceptible to many different infections o Any part of the body can get infected o Even before AIDS can fully develop, if a person gets a serious opportunistic infection they can die  AIDS dementia o Impairment of cognitive reasoning o Behavior changes o Sometimes when you get flu, you get so weak because your energy is so depleted  that can change your behavior too  When a person is infected the only way you can check if they are infected is by how many viruses are being made within the person o You can measure how many given virus particles are there per microliter of blood o Every person is different in their immunity  in some people the virus can replicate very rapidly, while in others it can replicate very slowly  Many drugs have been made o AZT – prevents the conversion of RNA to DNA  so DNA cannot get integrated into your chromosomes, but it is normal that people can develop resistance to any drug  People started to develop resistance to AZT o HAART – Highly Active Retroviral Therapy – mixture of three drugs, one is to block HIV reverse transcriptase, another inhibits protease activity (as a result the virus cannot assemble into mature virus), the other prevents the integration of the viral genome into the host chromosome (blocks integrase) o Fusion inhibitor prevents virus from fusing with the cell membrane so the virus cannot enter the host cell o All these drugs are used to attack the virus at different stages (attachment, assembly, etc.)  These drugs are not accessible to everybody because they are so expensive  To control viral diseases, a vaccine is the only way to actually cure a disease  A vaccine is nothing but a substance (like a protein) that the body recognizes and starts producing antibodies as a result, so that when a virus enters the body the antibodies are present to attack the virus  We need a vaccine because many of these major viruses have been cured only with the help of vaccines, not with drugs  Vaccines can only provide a successful cure  HIV vaccine is essential o Even a partially effective AIDS vaccine could save millions o HIV vaccine will not depend on consent of both sexual partners  Who are mostly affected/vulnerable to HIV/AIDS o Homosexuals o African Americans o Hispanics/Latinos  Conducted studies of HIV vaccine o Mixture of two antibodies o Must determine that the vaccine is successful and protects a wide range of people o Takes years to develop a vaccine o Some people may have extremely high immunity  it is possible that some person may even be completely immune to HIV o Vaccines can protect monkeys from SIV  Took 47 years to develop a polio vaccine  First they have to discover what criteria needs to be used to develop a vaccine  Must have human volunteers to test vaccine  A person will not get HIV from an HIV vaccine o Only inactivated viruses Virology Lecture 4/20/16  Oncogenic – causes tumors/cancers  HIV – Lentivirus (cone-shaped)  These retroviruses look like icosahedrals, but inside the entire capsid has a different shape depending on what the virus is  Inside the cone-shaped structure, HIV has 2 copies of the same RNA o No other viruses have 2 copies of the same RNA  Reverse transcriptase and integrase encoded  HIV-1 vs HIV-2 o Must enter through blood, or sexual transmission o HIV-1 is more prevalent throughout the world o HIV-2 present most often in Africa  HIV-2 is less easily transmitted than HIV-1  HIV-2 develops very slowly  Mother to child transmission is very rare with HIV-2  HIV targets the immune system (CD4)  Virus is extremely difficult to control because it attacks the immune system  the body cannot fight even minor infections  People do not die from HIV, they die from other infections because their immune system is compromised  HIV is not easy to treat with drugs  Treatment is expensive, and not readily available, and has side effects  Influenza has vaccinations available before flu season, but there are no drugs or vaccines that can protect you from getting infected with HIV  HIV is very unstable – once the virus leaves the host (blood on floor), the virus will die  You need a lot more virus particles to initiate the infection  Cannot be transmitted by air, water, food, contact, insects o ONLY transmitted via blood and sexual contact  Easily broken down by soap and antiseptics o This is very different from polio which is extremely stable and cannot be broken down by acids  10 Viral Replication Steps o This virus has a couple extra steps compared to other viruses because it has a DNA intermediate  Attachment o Very specific receptor cells on the virus (glycoprotein receptors)  HIV has co-receptors as well  CD4 main receptor  Co-receptors are CCr5 and CXCr4  Polio virus only has one receptor  sialic acid  T-cell uses CxCr4 receptor  Macrophages – any foreign material that comes is engulfed and killed  Macrophages use Ccr5 receptor  Once the virus is established and starts replicating very heavily a new virus species will develop (because a lot of RNA mutations will result  RNA Pol doesn’t have any proofreading mechanisms)  RNA Pol makes a lot of mistakes  in each round of replication 4 mutations are introduced  This means new viruses are being produced once HIV infects a host  Cell makes one large polyprotein  Integrase integrates the viral DNA into the host DNA  Every protein that is required for every stage is readily available for the virus once it is released into the host  Although RNAs are messenger sense, once they get released they do NOT get translated  they do NOT serve as mRNAs  this is a unique feature of HIV  Binds and penetrates using endocytosis  HIV has two RNAs, and it also encodes/packages tRNA from the cell o tRNA acts as a primer for RNA to get copied into DNA  Steps o Virus binds to the membrane, by endocytosis, and eters the cell o The RNA is used as a template to make +ssDNA o Now you have an RNA-DNA hybrid/copy o RNase H activity – specifically cleaves the RNA at certain places  Each piece functions as a primer o In the next step dsDNA is made o Once dsDNA is made, the virus carries integrase, takes the DNA to the nucleus, and ligates into the host chromosome o Using DNA Pol the dsDNA gets transcribed into RNA (HIV RNA) o The new viral RNAs are transcribed from the dsDNA integrated in the chromosome o Now that new RNAs are made they exit the nucleus, and enter the cytoplasm and gt translated  For TMV only one virus particle is needed to infect  For HIV many virus particles are needed to infect o But that is not a limiting factor because it is able to make so many  If you want to inhibit entry you need to inhibit ALL particles  if just one particle enters it will replicate into many  Protease inhibitors  once


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