Ned Landau joins the TWiV team to discuss restriction of HIV replication by SAMHD1, and a viral antagonist that can be used to produce a dendritic cell vaccine.
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Lemurs are primates found only on the island of Madagascar and a few small neighboring islands. Some of these animals have endogenous lentiviruses in their genomes. How did these viruses infect the isolated lemurs?
Madagascar split off from the African continent at least 100 million years ago, when there were no primates on Earth. Lemurs later appeared in Europe, North America, and Africa. They probably traveled from Africa to Madagascar when the island was not as far as it is today from Africa, on mats of vegetation flushed out of rivers. There they established and speciated (today there are 30 species of lemur on the island), while their ancestors elsewhere died out.
Lentiviruses cause chronic infections in a variety of mammals. The best known lentivirus is HIV-1, which has infected millions of humans and originated from the chimpanzee lentivirus simian immunodeficiency virus. It has been difficult to gauge the age of lentiviruses. Phylogenetic analysis of sequence data from lentiviruses can provide an idea of their recent history, but to trace further back – millions of years – requires the discovery of endogenous viruses integrated into the host cell genome. Up until 2007, no endogenous lentiviral genome had been found.
This situation changed in 2007 with the discovery of an endogenous lentivirus in the genome of the European rabbit. This finding made it possible to determine that lentiviruses are at least 7 million years old.
A year later, an endogenous lentivirus was discovered in the genome of the gray mouse lemur (pictured; image credit). Subsequently lentiviral insertions were discovered in the genomes of seven species of lemur from two different genera. These viruses are thought to have invaded the lemur genome approximately 4.2 million years ago – when the animals were firmly ensconced on Madagascar. How were they infected?
It’s possible that the lemur arrived on Madagascar already infected with lentiviruses, but they did not invade the genome until much later. Or that a lentivirus-infected primate arrived on the island after the lemurs and infected them; these hypothetical animals subsequently must have died out. Finally, a vector capable of traversing the 400 km distance from Africa to Madagascar might have brought the virus over.
Which of these scenarios is correct is unknown, hence how lemurs became infected with lentiviruses remains a mystery.
Vincent and Dickson travel to the 44th Retrovirus meeting at Cold Spring Harbor Laboratories, where they speak with John Coffin, Stephen Hughes, Ya-Chi Ho, and Matt Takata about the meeting and their work on HIV-1.
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Poliovirus by Jason Roberts
The global withdrawal of the Sabin type 2 poliovirus vaccine is a test of the feasibility of the plan, declared by the World Health Assembly in 1988, to eradicate all polioviruses.
The main vaccine used for the poliovirus eradication effort is an infectious, attenuated preparation called oral poliovirus vaccine (OPV), developed by Albert Sabin. Comprised of all three poliovirus serotypes, it is taken by mouth. During replication in the intestine, it confers immunity to infection and also changes genetically and re-acquires the ability to cause paralysis. These vaccine-derived polioviruses can circulate in the population and cause outbreaks of poliomyelitis.
The last case of paralysis caused by wild (e.g. non-vaccine) poliovirus type 2 occurred in 1999 in India. However, type 2 circulating vaccine-derived polioviruses (cVDPV) continued to cause outbreaks of poliomyelitis. Consequently it was decided, in 2016, to stop immunizing with type 2 OPV. This event was a test for the eventual cessation of immunization with all serotypes of poliovirus vaccine. The important question is whether VDPVs will continue to circulate and pose a threat long after cessation of vaccination, or will vaccine strains disappear?
A new study has provided some answers to these questions. From January 2013 through July 2018, stool samples from 495,035 children with acute flaccid paralysis in 118 countries, and 8528 sewage samples from four countries at high risk for poliovirus transmission were examined for the presence of type 2 OPV or type 2 cVDPV. Type 2 OPV declined in stools from 3.9% in 2016 to 0.2% within 2 months after withdrawal, but was still detected after 12 months.
The continued presence of type 2 OPV in stool can be ascribed to the use of the vaccine to stop outbreaks. After the withdrawal of type 2 OPV, there were 9 outbreaks caused by type 2 cVDPV. These outbreaks occurred in countries with low rates of immunization and consequently low population immunity against poliovirus. These outbreaks took place in the same areas as before the removal of type 2 OPV.
The good news is that all but two 2018 outbreaks in Nigeria were caused by type 2 cVDPV that had been circulating before withdrawal of type 2 OPV. The use of type 2 OPV to control outbreaks has not resulted in widespread circulation of the virus as feared.
It should be noted that the withdrawal of type 2 OPV was accompanied by the recommendation that a dose of trivalent inactivated poliovirus vaccine, a.k.a. Salk vaccine, be given. The use of type IPV should keep population immunity high, inhibiting the circulation of type 2 cVDPVs. Unfortunately due to supply shortages the use of type 2 IPV has not been as extensive as desired.
These findings suggest that circulation of type 2 VDPV can be limited if immunization rates are high in these key regions. Whether or not this goal can be achieved is not known – the areas with low population immunity against poliovirus are typically those with social conditions that prevent adequate vaccination.
The ability to screen thousands of stools and sewage samples and distinguish between type 2 OPV and VDPV is a result of the outstanding surveillance system put in place by the Global Polio Laboratory Network of the Global Polio Eradication Initiative. This system will be essential for monitoring the presence of type 2 polioviruses to determine when they are no longer present and all type 2 immunization can be stopped.
The eradication of wild type 3 poliovirus is imminent – no case has been detected since 2012. Only wild type 1 poliovirus remains – in 2017 there were 22 cases of poliomyelitis caused by type 1 poliovirus (in Afghanistan and Pakistan), and 96 cases caused by type 2 cVDPV. Based on the findings of the type 2 study described here, the withdrawal of both type 1 and type 3 OPV in the future can proceed, but only if high population immunity and careful poliovirus surveillance are maintained.
By David Tuller, DrPH
Cochrane–formerly called the Cochrane Collaboration–is respected worldwide for its systematic reviews of medical treatments. These reviews are often cited as the definitive source of information about treatment efficacy and safety. In taking on the thankless task of assessing the data on commonly used interventions, Cochrane performs an invaluable public health service and has advanced the cause of evidence-based decision-making in medicine.
The TWiV team considers whether those who can do, can’t teach, and newly discovered viruses of planarians and Aplysia with the largest RNA genomes.
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The development of high throughput nucleic acid sequencing tools has rapidly increased the pace of virus discovery in the past 20 years. Yet in that time, while the largest DNA genomes have increased by nearly ten times, the largest known RNA viral genome has only increase in size by a tenth. This situation has now changed with the discovery of new RNA viruses of planarians and mollusks.
By David Tuller, DrPH
Jonathan Edwards, an emeritus professor of medicine at University College London, recently sent a letter to Professor Fiona Watt, executive chairwoman of the UK Medical Research Council. The MRC was the main funder of PACE and has continued to defend the trial and its conduct. In recent years, Professor Edwards has been very involved in the effort to promote biomedical research and blunt the impact of PACE and related research. In his letter, he urged the MRC to publicly acknowledge that it was a mistake to fund the trial in the first place. Not surprisingly, Professor Watt declined to take such a step.
By David Tuller, DrPH
Last week, The Times ran an article about the open letter to The Lancet concerning the PACE trial, quickly followed by a piece in The BMJ. This morning, I e-mailed the following letter to Fiona Godlee, editor-in-chief of The BMJ and editorial director at BMJ. I cc’d officials at the Health Research Authority, some NICE stakeholders, and Carol Monaghan MP on the letter, since all have interests in the proper assessment of studies in this domain.
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Jens Kuhn returns to present a brief history of bioweapons, with a focus on the program in the Soviet Union, the largest ever undertaken, and his experience working in the decommissioned Soviet bioweapons laboratory known as Vector.
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