Interview with J. Michael Bishop

A major new feature of the fourth edition of Principles of Virology is the inclusion of 26 video interviews with leading scientists who have made significant contributions to the field of virology. For the chapter on Transformation and Oncogenesis, Vincent spoke with Nobel Laureate J. Michael Biship, of the University of California, San Francisco, about his career and his work on oncogenes.

TWiV 393: Lovers and livers

Possible sexual transmission of Zika virus, and a cell protein that allows hepatitis C virus replication in cell culture by enhancing vitamin E mediated protection against lipid peroxidation, are the subjects discussed by the TWiVerati on this week’s episode of the science show This Week in Virology.

You can find TWiV #393 at microbe.tv/twiv, or listen below.

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Zika virus and mosquito eradication

Aedes aegyptiThe Aedes aegypti eradication campaign coordinated by the Pan American Health Organization led by 1962 to elimination of this mosquito from 18 countries, including Brazil. Ae. aegypti transmits not only Zika virus, but dengue virus, chikungunya virus, and yellow fever virus. Could control measures be implemented today to achieve similar control of this mosquito? Two articles in PLoS Neglected Tropical Diseases revisit the successful PAHO mosquito control campaign and suggest that its approaches should be revived.

The elimination of Ae. aegypti in 18 countries, which was accompanied by a marked reduction in dengue hemorrhagic fever, was achieved by removing mosquito breeding sites or spraying them with DDT. Determining whether households harbored such breeding sites was essential for the effectiveness of the campaign.

The United States did not participate in the PAHO campaign, even though Ae. aegypti was (and still is) present in that country, and was a vector for outbreaks of dengue fever from the 1920s through the 1940s. Peter Hotez (link to paper) cites a “lack of funds and political will” and “logistical difficulties due to lack of access to private homes or cultural norms of privacy in the US”. As a consequence, by 1970 the US became one of the last reservoirs of Ae. aegypti in the Americas.

Eventually the PAHO campaign fell apart and Ae. aegypti returned, followed by outbreaks of dengue fever in the 1980s in Latin America and the Caribbean, and Chikungunya virus and Zika virus in 2013.

Hotez argues that while control of Ae. aegypti is labor intensive and involves house-to-house spraying, PAHO demonstrated its feasibility. He further suggests that by not participating in the PAHO campaign, the US failed to establish a generation of mosquito control expertise, which is now needed as Zika virus and other mosquito-borne viruses threaten to spread. He calls for an “unprecedented campaign against the Ae. aegypti mosquito”. However, he does not specify exactly what kind of control should be implemented, only saying that “these activities might not closely resemble the Latin American programs of the 1960s”.

Paul Reiter (link to paper) believes that the success of the PAHO campaign “can be attributed to a single aspect of the behavior of the mosquitoes: female Ae. aegypti do not lay all their eggs in one basket”, but rather place them at multiple locations. During the PAHO campaign, infested containers were identified and sprayed with DDT, increasing the likelihood that a female would lay eggs at a site that had been treated. This approach is called perifocal.

The current use of fogging machines to spray residential areas with insecticides has a low impact on mosquito populations, according to Reiter, because they only work for a few minutes when the droplets are airborne. He believes that we should return to perifocal treatments to eliminate mosquitoes, but not using DDT. Rather he suggests the use of other, novel insecticides, such as crystals of deltamethrin embedded in a rain and sun-proof polymer that ensures release for three months.

Reiter acknowledges that long-term use of insecticides leads to resistance, in which case we should turn to the new anti-mosquito approaches that are being developed, including the release of mosquitoes containing Wolbachia bacteria or a lethal gene. But he indicates that these approaches “are some way from mass application”, and meanwhile, perifocal approaches could reduce mosquito populations (although the newer insecticides would first need to be tested).

The best way to prevent viral infection is with a vaccine, but one for Zika virus is likely years away. Meanwhile, mosquito control can make a difference, as it could for the next emerging virus well before a vaccine can be developed.

Virus Watch: How mosquitoes spread viruses

In this episode of Virus Watch, I explain how mosquitoes spread viruses. We’ll look at how a mosquito finds a host, how it finds a blood vessel, and how it delivers viruses to a new host. Don’t blame mosquitoes for viral diseases: it’s not their fault!

TWiV 392: Zika virus!

Four virologists discuss our current understanding of Zika virus biology, pathogenesis, transmission, and prevention, in this special live episode recorded at the American Society for Microbiology in Washington, DC.

You can find TWiV #392 at microbe.tv/twiv, or listen/watch below.

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Virus Watch: Counting Viruses

In this episode of Virus Watch, I show how to do my favorite assay in all of virology – the plaque assay.

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TWiV 391: Whiter reefs, fresh breath

If you have always wanted to know what coral reefs and the human oral cavity have in common, listen as guests David Pride and Forest Rohwer talk about their work on the microbiomes and viromes of these two environments, and you’ll also understand why mucus is cool.

You can find TWiV #391 at microbe.tv/twiv, or watch or listen below.

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The Zika Effect

Zika virusHaving worked on viruses for over 40 years, I know a fair number of people in the field, and I am amazed at how many of them have started to work on Zika virus. What exactly is attracting virologists to this emerging virus?

There are probably many reasons why Zika virus would be of interest to a research lab – what I call the Zika Effect – but here are what I think are the three main factors.

First, Zika virus has become medically important in the past year, as it has spread globally and is infecting many people each day. There are many unanswered questions about the virus, and for a scientist, there is nothing better than unanswered questions (except maybe getting money to answer the questions – see below). Because the virus is causing human disease, these questions have an immediacy – such as, does the virus cause birth defects; does the virus cross the placenta, and if so, how; how does the virus enter the central nervous system and cause disease, to name just a few. Because of the nature of Zika virus infection, the virus has attracted not only virologists, but neurobiologists, cell biologists, developmental biologists, and structural biologists. In short: scientists love answering questions, and when it comes to Zika virus, they are not in short supply.

Second, Zika virus is not dangerous to work with – a biosafety level 2 laboratory (BSL-2) is all that is needed. Most virologists carry out their work under BSL-2 containment, so if you are working on influenza virus, poliovirus, herpesvirus, and a host of other viruses, you are ready to work with Zika virus. This situation is in contrast to that which took place in 2015 with the ebolavirus outbreak in west Africa. Work on ebolavirus must be conducted under BSL-4 containment – which few virologists have access to (for a look inside a BSL-4 laboratory, check out the documentary Threading the NEIDL). Consequently far fewer laboratories began work on ebolaviruses after that outbreak.

The third reason for the Zika effect is the reward: the promise of a publication in a high profile scientific journal, a promotion, a new job, and new grant funding for the laboratory. Not the purest motivation, but a reality: in the United States, government funding of scientific research has been flat for so many years that any new opportunity is seized. Many laboratories are on the brink of extinction and reach out to any funding opportunity. Few will admit that funding or publication drives their interest in Zika virus, but there is no doubt that it is a major factor. If research money were plentiful, and if luxury journals were not so tightly linked to career success, there would likely be fewer entrants in the Zika race. And a race it is – at least in these early days, when low-hanging fruit is ripe for picking, papers roll out on a weekly basis and it is difficult to compete without a large research group.

The fact that so many laboratories are working on Zika virus is not only impressive but encouraging: it means that the scientific establishment is flexible and nimble. There is no doubt that the more minds engaged on a problem, the greater the chance that important questions will be answered. But working on Zika virus is not for the faint of heart – which I document on a weekly basis in Zika Diaries, a personal account of our foray into this seductive virus.

Interview with Karla Kirkegaard

A major new feature of the fourth edition of Principles of Virology is the inclusion of 26 video interviews with leading scientists who have made significant contributions to the field of virology. For the chapter on Synthesis of RNA from RNA templates, Vincent spoke with Karla Kirkegaard, PhD, of Stanford University School of Medicine, about her career and her work on picornaviruses.