TWiV 237: Paleovirology with Michael Emerman

Episode #237 of the science show This Week in Virology was recorded at the Fred Hutchinson Cancer Research Center in Seattle, WA, where Vincent and Rich met up with Michael to talk about his work on the molecular and evolutionary basis of HIV replication and pathogenesis.

You can find TWiV #237 at

Hilary Koprowski, 96

Racaniello, Koprowski, KessinVirologist Hilary Koprowski died on 11 April 2013 at the age of 96. His main accomplishments are nicely summarized in the New York Times, but for a more comprehensive overview of his life, I highly recommend his biography Listen to the Music by Roger Vaughan. I did not have many opportunities to interact with Dr. Koprowski, but I did follow his work on poliovirus vaccines and I have a few reminiscences.

In the 1930s Max Theiler had found that propagating yellow fever virus in an unnatural host – the chick embryo – dramatically reduced its capacity to cause disease in humans. Theiler’s work (which garnered him a Nobel Prize) lead to the production of the infectious, attenuated yellow fever vaccine which helped to vastly reduce the global incidence of yellow fever. Koprowski was inspired by Theiler’s work and decided to take a similar approach to developing a poliovirus vaccine – his first efforts involved passage of a type 2 strain of poliovirus in mice and then in cotton rats. After passage in  rodents, the virus did not cause paralysis in monkeys. Koprowski tested the candidate vaccine strain in humans, and ultimately produced two other attenuated poliovirus strains. By the 1960s these attenuated poliovirus vaccine candidates had been tested in millions of humans. However, they were never licensed for use in the US. While Koprowski was carrying out his work, Albert Sabin was also developed attenuated vaccine strains of poliovirus. Both Sabin’s and Koprowski’s strains were tested side by side in a monkey neurovirulence test carried out by Joseph Melnick at Baylor University. Sabin’s virus strains were slightly more attenuated, and in 1961-62 those were selected for licensing in the US. Sabin’s oral poliovirus vaccines (OPV) have been the mainstay of the World Health Organization in its polio eradication campaign.

Koprowski’s polio vaccines were tested by human clinical trials, notably in the former Belgian Congo in 1957-58. It was subsequently suggested that this clinical trial initiated the AIDS pandemic. The idea, first proposed by Tom Curtis (19 March 1992 “The Origin of AIDS: A startling new theory attempts to answer the question, ‘Was it an act of God or an act of man?” Rolling Stone pp. 54–9, 61, 106, 108) and subsequently by Edward Hooper in ‘The River‘, was that Koprowski had propagated the vaccine strains in kidney cell cultures produced from locally captured chimpanzees. If these animals were infected with the precursor of HIV-1, simian immunodeficiency virus (SIV), then the virus might have entered the human population during the polio vaccine trials. This hypothesis was subsequently shown to be incorrect as phylogenetic analysis showed that the main group of HIV-1 viruses, the M group, clearly crossed from chimpanzees to humans in the early 1900s.

A committee was established to investigate the virological aspects of the HIV-polio vaccine controversy, and towards the end of its work I was asked to join. When it was discovered that samples of Koprowski’s polio vaccines were frozen at the Wistar Institute in Philadelphia, it was decided to determine whether these vaccines had been propagated in rhesus monkey or chimpanzee cells.

I was given the job of dividing and coding the samples. I met a representative of the Wistar Institute in the parking lot of a restaurant just off the New Jersey Turnpike, halfway between New York and Philadelphia. He handed me a white styrofoam box, packed with ice, that contained  vials of the Koprowski vaccine. To the uninformed observer, it might have looked like a drug exchange.

CHAT vialsI took the vials back to the lab (see photo), thawed them, separated them into aliquots, and gave each a code. I then returned them to the Wistar in the same way, after a second trip on the New Jersey Turnpike. The samples were sent to three different laboratories where experiments were done to determine the mitochondrial DNA type of the cells in which the viruses had been propagated (although the samples were free of cells, some mitochondrial DNA would still be present from virus induced cell lysis). The results, which have been published (reference one, two), clearly showed that the vaccines had not been grown in chimpanzee cells. I was pleased to have played a small role in this story.

Koprowski autograph

Although I had spoken with Dr. Koprowski several times on the telephone, I did not meet him until 2005 when he presented a talk on the history of rabies in the History of Science series at Columbia University Medical Center. I was his host for that visit, during which I was photographed with Dr. Koprowski and Dr. Rich Kessin, another Columbia professor. We invited Dr. Koprowski to dinner after the seminar but he declined, but he did want to have a drink together. After being warned by his driver not to keep him too late, we walked to a local bar and Dr. Koprowski ordered a Boodles gin martini. The bartender noted that he didn’t receive many calls for that brand. Dr. Koprowski said it was his favorite gin. We talked for a while and then returned Dr. Koprowski to his car for the trip back to Philadelphia. During his visit I had Dr. Koprowski autograph my copy of Listen to the Music (photo). He wrote: “To my friend Vince, with warmest regards, Hilary, 4/14/05.” It was the first and last time I saw him.

I would like to relate one last story which has nothing to do with me, but is irresistible. It takes place in the opening pages of Listen to the Music. Koprowski and his technician Thomas Norton are about to drink an early version of his attenuated polio vaccine. The virus has been passaged in rats and appears to be attenuated in monkeys. On a January day in 1948 Koprowski and Norton are in a laboratory at Lederle Laboratories in Pearl River, NY., where they are blending the brains and spinal cords of rats that had been infected with the vaccine strain virus. They both drink a milliliter of the cold, greasy, mix which flows thickly over their tongues and is difficult to swallow.

Here is the best part:

When he can speak, Norton asks, “Have another?”

“Better not,” Koprowski says. “I’m driving.”

TWiV 225: Transcripts from the inbox

On episode #225 of the science show This Week in Virology, Vincent, Rich, and Kathy read listener comments and questions on viral oncotherapy, science communication, a functional HIV cure in an infant, and much more.

You can find TWiV #225 at

Antimicrobial peptides induced by herpesvirus enhance HIV-1 infection

Langerhans cellsThe risk of being infected with human immunodeficiency virus type 1 (HIV-1) is substantially enhanced in individuals with other sexually transmitted diseases. For example, infection with herpes simplex virus type 2 (HSV-2) increases the risk ratio of acquiring HIV from 2 to 4. Explanations for this increased risk include direct inoculation of HIV-1 into the blood through genital ulcers, and the induction of inflammatory cells by HSV-2 which act as sites of replication for HIV-1. The results of infections carried out in cell culture suggest a biological mechanism for the enhancement of HIV-1 infection by HSV-2.

Langerhans cells (LC) are believed to one of the first cells in which HIV-1 replicates after sexual exposure. LCs are dendritic cells which patrol the mucosal epithelium, taking up and processing antigens and presenting them to T cells in the lymph nodes. These cells express the HIV-1 receptors CD4 and CCR5, but not CXCR4, and can therefore be infected with CCR5-tropic* but not CXCR4-tropic HIV-1. Individuals who do not express CCR5 are resistant to HIV infection. For these and other reasons CCR5-tropic HIV-1 viruses are believed to be ones that transmit infection from one individual to another.

In human skin explant cultures, which contain LCs, co-infection with HSV-2 substantially increased the number of HIV-1 cells. This observation could not be explained by co-infection of individual cells because very few of these were observed in the cultures. When applied to fresh cells, the supernatant of cultures infected with HSV-2 also stimulated the number of HIV-1 infected LCs. These observations suggested that HSV-2 infection stimulates the production of one or more substances from infected cells which in turn improve HIV-1 infection.

Human epithelial and epidermal cells are known to produce antimicrobial peptides such as defensins and cathelicidin. These are short, evolutionarily conserved peptides that inhibit the growth of bacteria, viruses, and fungi. HSV-2 infected keratinocytes were found to produce a number of antimicrobial peptides, but the most important one is called LL-37. This peptide enhanced the expression of HIV-1 receptors CD4 and CCR5 on LCs, leading to increased susceptibility of the cells to HIV-1. Removing LL-37 from the supernatant of HSV-2 infected cells reduces the ability of the medium to stimulate susceptibility to HIV-1.

These findings provide a plausible mechanism by which HIV-1 infection is enhanced by HSV-2. When HSV-2 infects the genital mucosa, the epithelial cells produce LL-37. This antimicrobial peptide enhances the production of CD4 and CCR5 on LCs, allowing more efficient infection by HIV-1. This mechanism is supported by the observation that elevated levels of LL-37 correlate with HIV-1 infection in sex workers.

I wonder why antimicrobial peptides up-regulate CD4 and CCR5. In addition to their antimicrobial properties, the cathelicidins possess chemotactic, immunostimulatory, and immunomodulatory effects, and the upregulation of CD4 and CCR5 are likely part of these activities.

These are exciting findings, and if they are further correlated in humans, they might lead to novel ways of interfering with HIV-1 infection, such as by antagonizing LL-37.

*CCR5 and CXCR4-tropic refer to HIV-1 virions that bind to chemokine receptors CCR5 or CXCR4, respectively, in addition to CD4, to initiate infection.

TWiV 219: Fauci pharmacy

Fauci PharmacyOn episode #219 of the science show This Week in Virology, Vincent and Rich meet up with Anthony S. Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases.

You can find TWiV #219 at

The AIDS pandemic

Origin of HIV

Any questions?

Viruses on Time

Poliovirus recently made the cover of Time magazine. Prompted by a reader question, I searched the Time archive to find out if there have been other virology-themed covers. I found fifteen in all, depicting poliovirus (3), herpesvirus (1), HIV/AIDS (4), influenza (5), and SARS coronavirus (2) (I did not distinguish between US and international editions).

The earliest virus-themed cover that I found has Jonas Salk on the cover of the 29 March 1954 issue. Behind Salk is an image of poliovirus particles, probably drawn from an electron micrograph. Salk’s field trial of inactivated poliovirus vaccine had begun in 1954, and in April of the next year the results would be announced:

Jonas Salk

John Enders made the cover of the 17 November 1961 issue, with poliovirions in the background. Enders had been awarded the Nobel Prize in 1954, along with Weller and Robbins, for being the first to propagate the virus in cell culture. This finding paved the way for Salk’s vaccine work.

John Enders

Viruses were not on the cover of Time for 23 years. The 2 August 1982 cover did not have a virus image, but touted herpes simplex virus as ‘Today’s scarlet letter”:


The 4 July 1983 cover featured disease detectives and AIDS:


AIDS returned on 12 August 1985, this time with an image of HIV:

AIDS threat

The 3 November 1986 cover featured the giant headline VIRUSES with a colorized scanning electron micrograph in the background. AIDS was also mentioned:


The Man of the Year for 1996 was virologist David Ho, who graced the cover of the 30 December 1996 issue, with virions reflected in his glasses. This is one of the coolest of the Time virus covers, in my opinion. Naming Ho Man of the Year was fully deserved and helped propel the virology field into the spotlight it deserved.

David Ho

The cover of the 23 February 1998 issue features the flu hunters and a background electron micrograph of influenza virus. This story followed the 1997 outbreak of influenza H5N1 in Hong Kong:

Flu hunters

The Hong Kong outbreak was also featured on the 9 March 1998 cover, with influenza virions in the green lettering:

Flu hunters 2

The SARS outbreak made the 5 May 2003 cover. There were two versions distributed in different countries:


SARS Nation

Avian influenza was later featured on two more covers, 9 February 2004 and 26 September 2005:

Bird flu

Death threat

The 2009 influenza H1N1 pandemic was on the cover of the 24 August 2009 issue:


And the latest virus on the cover is poliovirus, 14 January 2013:

Killing polio

Did I miss any?

The following covers did not feature viruses but were certainly relevant to virology. The antiviral interferon was featured on the 31 March 1980 issue:


Herbert Boyer, one of the pioneers of recombinant DNA technology, was on the 9 March 1981 issue:

Herbert Boyer

The 23 May 1998 cover featured a story on how the immune system fights off disease:

Immune system

Science under siege (sound familiar?) was the story on the 12 September 1994 issue:

Science under siege

The 12 September 1994 Time cover asked if we are losing the war against infectious diseases:

Killer microbes

 There have been 6,169 Time covers, and viruses have been featured on only fifteen. I understand that Time is not a science magazine, but I think it could do more for virology, and science in general (there were other science themed covers that I found, but not that many more).

I wonder how many viruses have been on the cover of Newsweek? Life Magazine? Scientific American?

HIV among US youth

The Centers for Disease Control and Prevention has released its latest estimates on the number of new HIV infections in the United States:

HIV remains a serious health problem, with an estimated 47,500 people becoming newly infected with the virus in the United States in 2010. Youth make up 7% of the more than 1 million people in the US living with HIV. About 12,000 youth were infected with HIV in 2010. The greatest number of infections occurred among gay and bisexual youth. Nearly half of all new infections among youth occur in African American males.

Included is this graph of at-risk populations:

At risk for HIV

Clearly awareness of HIV and how it is spread is not enough to prevent new infections. Would an effective HIV vaccine make a difference?

A pdf version of the factsheet is available for download.

Behind the scenes: TWiV 202 at the University of Nebraska

We recorded This Week in Virology #202 at the University of Nebraska in Lincoln, Nebraska on 5 October 2012, as part of the 12th Annual Symposium in Virology. Terence Dermody, Shou-Wei Ding, Grant McFadden and I spoke about our research, and then we recorded TWiV with University of Nebraska virologists James Van Etten, T. Jack Morris, and Charles Wood.

I was impressed by the fine virology being done at the Nebraska Center for Virology, as well as the collegiality of the virology community in Nebraska, Iowa, South Dakota, and Kansas – Symposium attendees were from all of those states! I met many young virologists at the poster session and I was touched by how many of them wanted to say hello and thank us for doing TWiV.

Many thanks to all the virologists who came to the Symposium and stayed to watch TWiV. Special thanks to Charles Wood, the Director of the Nebraska Center for Virology, who participated in TWiV #202 along with T. Jack Morris and James Van Etten.

Here are some behind the scenes photographs of this short but very informative visit.

TWiV 202: Huskers go viral

In episode #202 of the science show This Week in Virology, Vincent travels to the University of Nebraska to meet with members of the Nebraska Center for Virology and discuss their work on algal viruses, plant viruses, HIV and Kaposi’s sarcoma herpesvirus.

You can find TWiV #202 at