Understanding viruses

Virology lecturesIf you want to understand life on Earth, you need to know about viruses.

We have reached the halfway point in my 2016 Columbia University undergraduate virology course. So far we have learned the basics of virus replication: how viruses enter cells, how the genome is reproduced, and how proteins are made and assembled into new virus particles. In the second half of the course, we will consider how viruses cause disease, how immune responses prevent infection, vaccines, antivirals, emergence of new viruses, and much more.

All of my lectures are recorded as videos and available freely on YouTube. Below is a list of the first thirteen lectures, with links to the YouTube videos. You can also subscribe to the videos at iTunes University. If you would like copies of the lecture slides and study questions, go to virology.ws/course.

Lecture 1: What is a virus?
Lecture 2: The infectious cycle
Lecture 3: Genomes and genetics
Lecture 4: Structure
Lecture 5: Attachment and entry
Lecture 6: RNA directed RNA synthesis
Lecture 7: Transcription and RNA processing
Lecture 8: DNA replication
Lecture 9: Reverse transcription and integration
Lecture 10: Translation
Lecture 11: Assembly
Lecture 12: Infection basics
Lecture 13: Intrinsic and innate defenses


Earth’s virology course for 2016

Do you want to learn virology? Every spring I teach a virology course at Columbia University, and this year’s version has just started. I record every lecture and put the videos on YouTube. Here is a link to the playlist: Virology Lectures 2016. Lecture #1, What is a Virus, is embedded below as a teaser.

I strongly believe that the best approach to teaching introductory virology is by emphasizing shared principles. Studying the phases of the viral reproductive cycle, illustrated with a set of representative viruses, provides an overview of the steps required to maintain these infectious agents in nature. Such knowledge cannot be acquired by learning a collection of facts about individual viruses. Consequently, the major goal of my virology course is to define and illustrate the basic principles of animal virus biology.

You can find the complete course syllabus, pdf files of the slides, and reading at virology.ws/course.

My goal is to be Earth’s virology professor, and this is my virology course for the planet.

Virology for planet Earth

Virology 2015It is the first week in May, which means that the spring semester has just ended at Columbia University, and my annual virology course is over.

Each year I teach an introductory undergraduate virology course that is organized around basic principles, including how virus particles are built, how they replicate, how they cause disease, and how to prevent infections. Some feel that it’s best to teach virology by virus: a lecture on influenza, herpesvirus, HIV, and on and on. But this approach is all wrong: you can’t learn virology by listening to lectures on a dozen different viruses. In the end all you will have is a list of facts but you won’t understand virology.

I record every one of my 26 introductory lectures as a videocast, and these are available on the course website, or on YouTube. If you have listened to my lectures before, you might be wondering what is new. I change about 10% of each lecture every year, updating the information and adding new figures. This year I’ve also added two new lectures, on on Ebolavirus and one on viral gene therapy.

Once you have taken my introductory course, then you will be ready for an advanced course on Viruses. A course in which we go into great detail on the replication, pathogenesis, and control of individual viruses. I am working on such a course and when it’s ready I’ll share it with everyone.

I want to be Earth’s virology professor, and this is my introductory virology course for the planet.

Ebola virus arrives in New York City

This morning I received this email from President Lee Bollinger:

Dear fellow members of the Columbia community:

As you may have seen in the media, Dr. Craig Spencer is being treated for Ebola at Bellevue Hospital in Manhattan. Dr. Spencer, an emergency department physician at NewYork-Presbyterian/Columbia University Medical Center, recently returned from a humanitarian mission with Doctors Without Borders to one of the outbreak areas in Western Africa. We admire and appreciate all of those willing to do this vital and selfless public health work around the globe.

It’s critical to bear in mind what our public health and infectious disease experts have emphasized – that the risk to people in New York City and at Columbia remains extremely low. If you or anyone has any concerns, please visit the University’s Ebola Preparedness site or the New York City Department of Health Ebola update page. You may also contact Student Health Services or Workforce Health and Safety for Faculty/Staff with Hospital Responsibilities.

We must keep Dr. Spencer in our thoughts and wish him a full and speedy recovery, as we do the vulnerable populations he serves. We will also continue to keep the Columbia community informed as we learn more from City, State, and Federal health officials.

Lee C. Bollinger

The transition between incubation period (when there are no symptoms) and the first clinical signs is a dangerous period. During this time the patient may continue to move around in public despite having fever and other indications of infection. It will be important to trace as many of this physician’s contacts as possible, a difficult task in a city of over 8 million people. Apparently the physician traveled around the city, using the subways, the night before having a fever. Whether any virus is shed during this time, in amounts sufficient to infect others, is unknown, but could be determined by studying the contacts of such infected individuals.

Twenty-six lectures in virology

Virology class 2014In the spring of each year I teach a virology course to undergraduates and masters students at Columbia University. I produce video recordings of all my lectures not only for students in the course, but for anyone else who is interested in learning about viruses.

You can find my virology lectures in several locations: at this blog and at iTunes University, where lecture slides are also available as pdf files, or at YouTube.

This is the fifth year that I have taught my virology course (current class is in the photo), and every version is different. This year, in addition to updating the material, I’ve added a new lecture on viral gene therapy, and include new lectures on immune defenses, viral virulence, acute and persistent infections.

The goal of my virology course is to provide an understanding of how viruses are built, how they replicate and evolve, how they cause disease, and how to prevent infection. The first half of the course explores the viral replication cycle, including attachment and entry, genome replication, protein synthesis, and assembly. In the second half of the course we explore viral pathogenesis: how viruses cause disease, defenses against infection, antivirals, vaccines, and much more. After taking the course, some students might want to become virologists. The course will also provide the knowledge required to make informed decisions about health issues such as immunization against viral infections.

If you have read this blog in the past you know that it is my goal to be Earth’s virology professor. I also teach two virology courses at Coursera (these are completed but the material is still accessible), and my colleagues in Mexico have translated my 2012 lectures into Spanish. Next year I plan to each a new virology course, focused on individual viruses, which will build upon knowledge obtained in my first offering – and of course you will be able to find the lectures online.

New media publishing: Whither the textbook?

The theme of a recent New Media in Education Conference held at Columbia University was how digital media has reshaped the traditional academic publishing paradigm. I participated in a session entitled ‘New media publishing: Whither the textbook?‘ in which four panelists spoke about their experiences in this area. I spoke about how I use podcasting, blogging, and online courses to teach the public about virology. Paulette Bernd discussed the iPad dissection manual she developed for use in the Gross Anatomy laboratory at the College of Physicians & Surgeons of Columbia University. Grant Ackerman detailed the Business School’s integration of iPads in the MBA program and their use of the iBook as an extended learning resource. Mark Newton recounted how the Center for Digital Research and Scholarship partners with Columbia faculty to implement innovative digital tools and publishing platforms for content delivery and preservation.

A virology course for all

Virology class 2013The spring semester has begun at Columbia University, which means that it is time to teach my virology course.

The fourth annual installment of my virology course, Biology W3310, has begun. This course, which I taught for the first time in 2009, is intended for advanced undergraduates and convenes at the Morningside Campus. Until I started this course, no instruction in virology had been offered at the Morningside Heights campus of Columbia University since the late 1980s. This is a serious omission for a first-class University. Sending graduates into the world without even a fundamental understanding of viruses and viral disease is inexcusable.

Course enrollment has steadily increased: 45 students in the 2009, 66 students in 2010, 87 students in 2012 and an amazing 195 students this year. I am gratified that so many students want to learn about the world of viruses. This year our class was moved into a wonderful lecture hall in the brand-new Northwest Corner building.

Readers of virology blog can watch every lecture in the course. You will find a videocast of each lecture at the course website, at my YouTube channel, and at iTunes University. The complete 2012 version of this course is available online, at iTunes University, and YouTube.

This year we will also be offering my virology course at Coursera. Details will be forthcoming.

To those who would like to know if the 2013 version of my course differs from the 2012 version, I reply: do viruses change? Some parts will be the same, others will be different. The goal of my virology course is to provide an understanding of how viruses are built, how they replicate and evolve, how they cause disease, and how to prevent infection. After taking the course, some of the students might want to become virologists. The course will also provide the knowledge required to make informed decisions about health issues such as immunization against viral infections. It should also be possible to spot badly constructed headlines about virology stories.

I am excited about teaching virology to 195 Columbia University students this year. But the internet makes it possible to spread the word even further. So far nearly 75,000 students registered for the iTunes University version of my 2012 virology course! As a professor used to teaching relatively small numbers of students in a classroom, this reach is truly amazing.

Thirty years in my laboratory at Columbia University

Racaniello labThirty years ago this month I arrived in the Department of Microbiology at Columbia University’s College of Physicians and Surgeons (P&S) to start my own laboratory. Thirty is not only a multiple of ten (which we tend to celebrate), but also a long time to be at one place. It’s clearly time to reminisce!

After studying influenza viruses with Peter Palese in New York City, in 1979 I headed to David Baltimore‘s laboratory at MIT. It was not long after Baltimore had received the Nobel Prize in Physiology or Medicine for discovering retroviral reverse transcriptase. In his laboratory I first encountered poliovirus, which would hold my interest for many years to come. The moratorium on recombinant DNA research had just been lifted, and it was now possible to clone complete viral DNA genomes. My first project was to make a DNA copy of poliovirus RNA, clone it into a bacterial plasmid, and determine its sequence. The result gave us the first glimpse of the viral genome. I then found that a DNA copy of poliovirus RNA is infectious in mammalian cells, a story that I have documented elsewhere.

The next step in my career was to have my own laboratory. With these two papers in hand I was able to obtain several respectable job offers, including one in the Microbiology Department at P&S. The department chair was Harold S. Ginsberg, an adenovirologist. My decision to accept his offer was influenced by the strong virology component of the department, which included Saul Silverstein and Hamish Young. I moved back to New York City in September 1982 with a DNA copy of the poliovirus genome in hand. In the last few weeks in the Baltimore laboratory, I had cloned a DNA copy of another poliovirus strain – type 2 Lansing – which had the interesting ability to infect mice. I spent the first few years in my new laboratory studying this virus and how it caused paralysis in mice. We found that the type 2 Lansing viral capsid was important for the ability to infect mice. Later, we narrowed this down to 8 amino acids. The type 1 Mahoney strain of poliovirus – which I had studied in the Baltimore laboratory – cannot infect mice. However, if we substituted 8 amino acids of the Mahoney capsid with the corresponding sequence from the Lansing genome, the recombinant virus could infect mice.

Our sequence analysis of poliovirus RNA had revealed an unusually long 5′-noncoding region. We began to carry out experiments to understand how such a viral RNA could be translated, and found that this long sequence enabled translation in the absence of a cap protein. This observation lead to the discovery by others that the poliovirus 5′-noncoding region contains an internal ribosome entry site (IRES). In the ensuing years our interest in translation continued. Examples include our finding that cell proteins bind to the poliovirus 5′-noncoding region, now known to participate in regulation of translation and genome replication, and understanding the inhibition of cell translation by poliovirus. Years later we developed a functional assay for the IRES in yeast, allowing identification of cell proteins needed for internal ribosome binding.

There is one area of research that has received the most attention in my laboratory, and on which we have published most extensively: the interaction of viruses with cell receptors. Towards the end of my stay in the Baltimore laboratory I became interested in how poliovirus attaches to and enters cells.  I came to Columbia with a strong interest in identifying the cell receptor for poliovirus, which we subsequently achieved. This finding lead to a series of studies on virus attachment to cells and virus entry. We produced transgenic mice susceptible to poliovirus, and used them to study aspects of poliovirus replication and pathogenesis, including how the virus attaches to its cellular receptor, regulation of viral tissue tropism, and the basis for attenuation of the Sabin vaccine strains.

The finding that poliovirus tropism is regulated by the interferon response lead to a change in the direction of our research. Beginning in the early 2000s we began studying how poliovirus interacted with the innate immune response. We found that poliovirus is relatively resistant to the antiviral effects of interferon, a property conferred by the viral 2Apro proteinase. How poliovirus is sensed by the innate immune system has also become a focus of our work. With the looming prospect of poliovirus eradication, and subsequent prohibition of work on the virus, we have also turned our attention to rhinoviruses, agents of respiratory illness. One focus has been to establish a mouse model for rhinovirus infection.

This story would not be complete without mentioning my foray into science communication. I have written a virology textbook and a blog about viruses, and began three science podcasts, including This Week in Virology, This Week in Parasitism, and This Week in Microbiology. My use of social media to teach microbiology to the world has been documented in a Social Media and Microbiology Education and in my Peter Wildy Prize Address.

None of this work would have been possible without the participation of 24 Ph.D. students (Nicola La Monica, Cathy Mendelsohn, Eric Moss, Robert O’Neill, Mary Morrison, Ruibao Ren, Elizabeth Colston, Michael Bouchard, Suhua Zhang, Alan Dove, Sa Liao, Yanzhang Dong, Yi Lin, Brian McDermott, Melissa Stewart Kim, Steven Kauder, Julie Harris, Amy Rosenfeld, Juliet Morrison, Angela Rasmussen, Jennifer Drahos, and Esther Francisco), 7 postdoctoral fellows (Gerardo Kaplan, Marion Freistadt, Michael Shepley, Ornella Flore, Juan Salas-Benito, and Scott Hughes), and many technicians and undergraduate students. My laboratory currently consists of postdoctoral scientist Rea Dabelic, and graduate students Ashlee Bennett and Michael Schreiber (pictured above).

Counting my time here, together with my Ph.D. and postdoctoral years, I’ve been working on viruses for 37 years. I do not know how much longer I will be doing the same, but it’s safe to say that it won’t be for another 37 years. But whenever I stop directing virology research, I will continue to write, podcast, and teach – you can expect nothing less from Earth’s virology professor.

Earth’s virology professor

w3310 virology 2012Nearly four months ago I stood at the front of a crowded classroom at Columbia University and began teaching the third year of my undergraduate virology course. Twice a week we discussed the basic principles of virology, including how virions are built, how they replicate, and how they cause disease. Yesterday was the 26th and last lecture in the course, entitled “H5N1”. In this lecture we covered the recent controversy over the publication of results on adapting avian influenza H5N1 viruses to transmit by the airborne route among ferrets. Fittingly, one of the two papers in question will be published tomorrow.

Each lecture in my virology course has been recorded as a videocast and is available at the course website, at iTunes University, or on Vimeo. Eighty-seven Columbia University undergraduates registered for the course in 2012, but over 14,000 individuals have subscribed to virology W3310 through iTunes University. I believe that it is important that the general public understand as much as possible about viruses, so they can participate in the debate about issues that impact them, such as XMRV or H5N1. It is my goal to be Earth’s virology professor.

I am sure that the students were perplexed when I took their photo before the first lecture. Little did they know that they were about to take a very different science course, one taught by a professor who uses social media (blogs, podcasts, twitter) to teach the subject both in and out of the classroom. As one student wrote to me yesterday:

I wish that every professor I had had such passion and energy and a TWiV-like blog/show so I could be updated on all the big science gossip/news to complement my in-class knowledge! I can’t recount how many times I told my non-science friends about TWiV as an exhibit to prove that science is cool and important. Thank you for being passionate scientists that made me want to study science (and be super nerdy but connected to the world) in the first place.

I would like to thank all the students of virology in and out of the classroom for their enthusiasm and their willingness to learn a complex subject. Virology will be offered again in the spring of 2013, and you can be reassured that it will be different. My course, like viruses, is continually evolving.

Virology course at halfway point

virology courseIt is spring break for students at Columbia University, which means that my annual virology course is one lecture past the halfway point. The first eleven lectures addressed basic aspects of viral replication in cell culture, including virus entry into cells, genome replication, and assembly. From this point onwards we will be discussing viral infection of a host, including pathogenesis, immunity, immunization, antivirals, and evolution.

All my virology lectures are available as videocasts (slides and audio) either at the course website, or at the new iTunes University.