TWiV 499: Good virologists go to Halifax

Vincent and Alan travel to the Canadian Society for Virology meeting in Halifax, Nova Scotia to speak with Nathalie and Craig about their vision for the society, and with Kate and Ryan about their careers and their research.

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Venezuela is still polio-free

AFP surveillance in Pakistan

AFP surveillance in Pakistan. Image credit.

In early June it was widely reported that the first case of poliomyelitis in 30 years had been identified in Venezuela (see this Tech Times report as an example). Fortunately these reports were incorrect, and Venezuela remains free of polio. Let’s unpack exactly what happened.

In early June the Pan-American Health Organization reported that on 29 April 2018 a 34 month old Venezuelan child developed acute flaccid paralysis (AFP). AFP is defined as a sudden onset of paralysis/weakness in any part of the body of a child less than 15 years of age.

AFP has many causes, only one of which is poliovirus infection. About 50,000 cases of AFP are reported each year in India, even though polio was declared eradicated from that country in 2014.

AFP surveillance is used as part of the poliovirus eradication effort to identify cases of polio. When cases of AFP are detected, a stool sample is taken to determine if poliovirus is present. In the case of the Venezuelan child, Sabin poliovirus type 3 was isolated from the stool.

This child had not been previously immunized with Sabin vaccine, so why was the virus present in the stool? Sabin’s poliovirus vaccines are taken orally – hence the name oral poliovirus vaccine (OPV). As in a natural poliovirus infection, Sabin’s vaccines replicate in the intestinal tract and induce protective immunity there and in the bloodstream. Sabin produced these vaccine strains by passaging polioviruses in different animals and cells until viruses were obtained that no longer cause paralysis.

We now understand that recipients of OPV may excrete, within a few days, viruses that are more neurovirulent that the vaccine strains. During replication of the OPV strains in the human intestine, the viral genome undergoes mutation and recombination that eliminate the attenuating mutations that Sabin so carefully selected by passage in different hosts.

Such reversion to neurovirulence of the Sabin OPV strains can cause polio in vaccine recipients or their contacts. For example, from 1961 to 1989 in the US there were an average of 9 cases (range, 1-25 cases) of vaccine-associated paralytic poliomyelitis (VAPP), or 1 VAPP case per 2.9 million doses of OPV distributed.

As wild type polioviruses are eliminated, most of the cases of polio are caused by the vaccine: in 2017, there were 96 cases of VAPP and 22 caused by wild type poliovirus.

Here is the crux of the matter: vaccine-derived polioviruses can circulate in humans for many years undetected. When polio immunization coverage drops, these circulating vaccine-derived polioviruses can cause outbreaks of poliomyelitis.

The combination of lack of immunization of the child, the finding of AFP and Sabin type 3 OPV in the stool led to the erroneous conclusion by many (including me!) that this was a case of VAPP.

Determination of the nucleotide sequence of the Sabin type 3 poliovirus isolated from the child’s stool revealed it did not have the mutations known to cause VAPP.

How can this conclusion be made from the viral genome sequence?

As Sabin polioviruses replicate in the human intestine, are excreted, and spread in the population, they sustain genome mutations at a rate of about 1% per year. This mutation rate makes it possible to determine how long the viruses have been circulating in humans. Some of these mutations are known to restore the ability of the virus to cause paralysis. Examination of the genome of the virus isolated from the child indicated that is was very much like Sabin 3 poliovirus, and does not have the capacity to cause polio (I’ve not seen the sequence myself, so I have to take the word of the Global Polio Eradication Initiative).

The Venezuelan child had never received any type of poliovaccine, and lived in an under-immunized community. A mass vaccination campaign, using Sabin types 1 and 3 poliovaccine, had been done a few weeks before the onset of AFP. The child likely acquired Sabin 3 poliovirus from that immunization campaign, which coincided with the development of AFP. Sabin polioviruses are isolated from thousands of individuals each year who have AFP, but they are not the causative agents. The actual cause of AFP will likely never be known.

Had this been a case of poliovirus type 3 VAPP in an under-immunized area, it would have been bad news. How could we ever stop vaccinating against polio if infections can occur 30 years after the declaration of eradication?

The fact that immunization rates have fallen in parts of Venezuela is the real story here. As long as we are using Sabin OPV, immunization rates must remain high, to protect against VAPP. Meanwhile, the transition to the use of inactivated poliovaccine must be done to eliminate the threat of VAPP. As long as we use Sabin OPV, we cannot eradicate poliovirus.

TWiV 498: Salivating at ASM Microbe

Vincent, Kathy and Rich travel to ASM Microbe 2018 in Atlanta where they speak with Stacy Horner and Ken Stapleford about their careers and their research.

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A Mouse Model System for Zika Virus Infection

IFN signaling

Type I IFN receptor binding and signal transduction.

By Gertrud U. Rey

Zika virus (ZIKV) infection causes microcephaly in newborns and is causally associated with Guillian–Barré syndrome in adults. To date, there are no drugs available to prevent or treat ZIKV infection. ZIKV vaccine research is challenging because adult immunocompetent mice are resistant to ZIKV infection and disease.

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TWiV 497: Europic 2018

At Europic 2018, a meeting on picornaviruses in the Netherlands, Vincent speaks with Sasha Gorbalenya, Jim Hogle, Ann Palmenberg and Frank van Kuppeveld about their careers and their research.

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Blocking rhinovirus infection by inhibiting a cell enzyme

N-terminal myristoylation

N-terminal myristoylation. An amide bond links myristate to an N-terminal glycine in the myristoylation site consensus sequence.

The common cold is an infection of the upper respiratory tract that may be caused by many different viruses, but most frequently by rhinoviruses. A compound that inhibits a cell enzyme and blocks rhinovirus replication has the potential to be developed into an antiviral drug (link to paper).

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TWiV 496: Vaccines work, whether or not you believe in them

Vincent and Rich recorded this episode at Vaccines in the 21st Century, a meeting held at the University of California, Irvine, where they spoke with Stacy Schultz-Cherry, Douglas Diekema, and Andrew Noymer about vaccine facts and fiction.

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Living on the edge of parasite inevitability

All life forms on Earth harbor an array of genetic parasites, including viruses, plasmids, and transposons. Unfortunately, if cells could reduce their uptake of these elements, they would suffer as the entry of beneficial genes would be impaired (link to paper). In other words, genetic parasites are unavoidable.

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TWiV 495: Influenza virus keeps its ion channel 20

The TWiVerati follow up on the Ebola virus outbreak, virulence of Ebola-Makona, and reveal how a parasitoid is revealed to hyperparasitoids, and binding of influenza virus to a calcium ion channel to mediate influenza virus entry.

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A Live-Attenuated Herpes Simplex Virus Vaccine Candidate

herpesvirusBy Gertrud U. Rey

There is currently no vaccine to prevent infection with herpes simplex virus type 1 or type 2 (HSV-1 or HSV-2). Infection with either of these viruses results in life-long viral latency. Sporadic reactivation and viral shedding may lead to painful oral and genital disease and an increased risk of HIV transmission.

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