Virology
Video Lectures
Displaying all 26 video lectures.
Lecture 1![]() Play Video |
What is a virus? In this first lecture of my 2016 Columbia University virology course, we explore the definitiions of viruses, their discovery and properties, and my goals for this course. |
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The Infectious Cycle The infectious cycle is the name for the entire sequence of events from virus binding to cells to release of new progeny virus particles. In this lecture we define the infectious cycle, and discuss how to study it. We cover assay of infectious virus particles by plaque assay, multiplicity of infection, and the particle to pfu ratio. We also discuss physical methods for detecting viruses including hemagglutination, polymerase chain reaction, and deep, high-throughput sequencing. |
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Genomes and Genetics There are billions and billions of viruses on Earth, but only seven different types of viral genome. In this lecture we go over each genome type and trace the pathway to mRNA. We discuss the largest and smallest genomes, what is and is not encoded in the genome, and how to manipulate the genome to study viruses and make them into vectors for therapy. |
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Structure of viruses Virus particles are built to protect the genome and to deliver it to a new host cell. In this lecture we consider the two main ways that viruses are constructed, by helical and icosahedral symmetry. We discuss how to make larger and larger viruses, the triangulation number, quasiequivalence, and metastability. We end with a discussion of the lipid envelope derived from the host cell that is embedded with viral glycoproteins. |
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Attachment and Entry As obligate intracellular parasites, viruses must enter cells to replicate. They cannot simply pass through the cell membrane, but rather enter cells by receptor mediated entry. In this lecture we discuss how icosahedral and enveloped viruses attach to cell receptors, how the nucleic acid enters the cell, and how uncoating is regulated. |
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RNA Directed RNA Synthesis In our virology series we now move into synthetic mode, as RNA viruses carry out synthesis of mRNAs and viral genomes. It all starts with the RNA dependent RNA polymerase, encoded in the viral genome. We'll see how RNA synthesis is primed, what controls the switch from synthesis of mRNAs to genomes, and how dsRNA viruses never release their genomes into the cytoplasm. We conclude with a brief visit to the amazing world of non-templated RNA synthesis. |
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Transcription and RNA Processing When DNA viruses enter cells, the first biosynthetic step that takes place is synthesis of mRNAs for translation into protein. In this lecture, we discuss the enzymes that carry out this reaction, regulation of the process by viral proteins, positive feedback loops and transcriptional cascades, and RNA processing, the addition of 5'-cap, poly(A) tail, splicing, and RNA export. |
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Viral DNA Replication Every known DNA virus must make at least one protein to allow genome replication to take place. In this lecture we cover how DNA viruses replicate their genome, including replication by strand displacement or a replication fork, solving the 5'-end problem of RNA priming, how genomes of different structures are copied, and how viruses make sure cells are actively duplicating their DNA to provide access to the DNA synthesis machinery. |
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Reverse transcription and integration Retroid viruses have the enzyme reverse transcriptase as part of their replication cycles. This enzyme, whose discovery by Temin and Baltimore shattered the dogma about the information flow in biological systems, produces DNA from RNA. In this lecture we discuss the discovery of reverse transcriptase in the context of RNA tumor viruses, the mechanism of reverse transcription and integration, and its role in the cycles of retroviruses and hepatitis B virus. We also consider the origin and functions of retroelements in the genome, mobile sequences that move about through the action of reverse transcriptase. |
Lecture 10![]() Play Video |
Lost in translation Because viruses cannot do protein synthesis, they must produce mRNAs that can be translated by the host cell machinery. However, virus infections can alter the translational landscape to favor the production of viral proteins, and to make more than one protein from single RNAs. In this lecture we consider how viral translation differs from that of the host, how to overcome the eukaryotic one mRNA-one protein limitation, and modulation of translation by host and virus. |
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Assembly Our travel through the viral replication cycle ends with a discussion of how virus particles are built. Viruses are assembled by a sequential or concerted process, usually by first making sub-assemblies. Viral nucleic acids are incorporated preferentially by packaging sequences on viral genomes. An envelope is acquired during the budding process when the ESCRT pathway of the cell is usurped. And non-enveloped viruses leave cells by breaking them open, or by surreptitiously acquiring an envelope. |
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Infection Basics In the real world, as opposed to the laboratory, viruses must establish a chain of infection among hosts, otherwise they will disappear from the planet. While many virus infections are inapparent, those that cause disease have our attention. In this lecture we consider how viruses enter the host, spread to different tissues, and transmit to new hosts. We also consider how geography and season may affect virus infections. |
Lecture 13![]() Play Video |
roviral Reverse Transcription The process of reverse transcription of the retroviral RNA genome to form a DNA copy is a bit confusing, so I created this animated short video that might help in understanding the different steps. |
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Intrinsic and Innate Defenses In this and the next lecture, we discuss the myriad defenses on and in a animal host that are engaged upon encounters with viruses. If a virus gets past the chemical and physical defenses of the host, next in its way stands intrinsic defenses (always present in the cell), and then innate defenses (which must be induced by infection). Both are highly effective antiviral systems, but are antagonized by many different viral proteins - and this is one reason why viruses are successful at being maintained in populations. |
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Adaptive Immunity When intrinsic and innate immunity cannot stop a virus infection, who you gonna call? Adaptive immunity, in the form of antibodies and T cells. In this lecture we examine how the innate immune system calls for help, how antibodies and T cells are made, and how they prevent and resolve virus infections. |
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Mechanisms of Pathogenesis An important goal of virology research is to understand viral pathogenesis - how viruses cause disease. In this lecture we discuss methods for studying pathogenesis, viral and host genes that regulate development of disease, how the immune response may cause disease, and determinants of susceptibility and resistance. |
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Acute Infections Human viral infections follow one of two patterns: acute and persistent. In this lecture we define an acute infection, the incubation period, and asymptomatic infections, and discuss why these are public health problems. Then we illustrate acute infections with five examples: influenza virus, poliovirus, measles virus, norovirus, and West Nile virus. |
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Persistent Infections Persistent viral infections begin with an acute infection that is never cleared by the immune system, and last the lifetime of the host. In some persistent infections viruses are continuously produced with no disease. In latent persistent infections the viral genome is always present but production of virus particles alternates with absence of virus production. In this lecture we consider examples of persistent human infections, including those caused by polyomaviruses, hepatitis viruses, and herpesviruses. |
Lecture 19![]() Play Video |
Transformation and Oncogenesis The road to understanding the control of cell growth, and how it is altered in cancer, is paved with RNA and DNA tumor viruses. Starting with Peyton Rous and his retrovirus that causes tumors in chickens, we move through the discoveries that revealed how photo-oncogenes regulate the mitogenic cycle, and the DNA tumor viruses that push cells through mitosis so they can replicate their genomes. These studies reveal how viruses transform cells - putting them on the road to cancer. |
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Vaccines Vaccines are a proven way to prevent viral infections. In this lecture we consider examples of different types of vaccines and how they work, including inactivated vaccines, subunit vaccines, and replication competent, infectious vaccines. We also discuss how vaccines work, and the properties of an ideal vaccine. |
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Antivirals Vaccines can prevent disease, but they have little effect if an individual is already infected (the exception is rabies). Our second arm of defense is antiviral drugs.How antiviral drugs are discovered, mechanisms of action of currently licensed compounds, and the problems of drug resistance are the topics of this lecture. |
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Evolution Charles Darwin would have loved viruses! They epitomize evolution by natural selection, and for RNA viruses, this process happens so quickly that it can be observed in real time. In this lecture you will learn all about how viral evolution works - what creates viral diversity, and how selection works. We'll explore the evolution of viral virulence, and the origin of viruses. |
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Emerging Viruses An emerging virus is the agent of a new or previously unrecognized disease. Today non-human animals are the main sources of new infections caused by viruses such as Lass virus, Ebola virus, and Zika virus. After listening to this lecture you will understand about the different types of virus-host interactions, what conditions lead to new virus emergence, and how Ebolaviruses and Zika virus emerged and spread. |
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Unusual infectious agents What is the smallest genome that can sustain an infectious agent? Could an infectious agent exist without a genome? These questions are answered by the amazing viroids - small RNAs that encode no proteins, satellites, and prions - infectious proteins that cause disease. |
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HIV and AIDS HIV-1 originated from crossovers of simian viruses from chimps and gorillas to humans. From four separate crossover events emerged viruses that have infected and killed millions. In this lecture we consider the origin of HIV, how it was discovered, the pathogenesis of infection, and prospects for prevention. |
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Viral gene therapy Fundamental knowledge about viral genomes, replication, and interaction with the host can be harnessed to produce vectors for treatment of human diseases. Applications of viral vectors include immunization against viral disease, monogenic gene therapy, and oncotherapy. In this lecture we describe different viruses used for gene therapy, how they work, and examples of their applications. |