TWiV 390: Building a better mosquito trap

TWiVProject Premonition, a Microsoft Research project that uses drones to capture mosquitoes and analyze them for pathogens, preprint servers, and three mouse models for Zika virus induced birth defects are the topics of episode #390 of the science show This Week in Virology.

You can find TWiV #390 at microbe.tv/twiv, or listen below.

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TWiV 388: What could possibly go wrong?

TWiVPreprint servers, the structure of an antibody bound to Zika virus, blocking Zika virus replication in mosquitoes with Wolbachia, and killing carp in Australia with a herpesvirus are topics of episode #388 of the science show This Week in Virology, hosted by Vincent, Dickson, Alan, and Kathy.

You can find TWiV #388 at microbe.tv/twiv, or listen below.

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Zika virus in Brazilian non-human primates

Callithrix jacchusZika virus RNA has been detected in New World monkeys from the Northeast region of Brazil. This finding suggests that primates may serve as a reservoir host for the virus, as occurs in Africa.

The results of numerous serological surveys have shown that different Old World monkeys in Africa and Asia, including Rhesus macaques, Grivets, Redtail monkeys, and others, have antibodies that react with Zika virus. In these areas Zika virus is probably transmitted among monkeys in what is called a sylvatic cycle. Periodic outbreaks (epizootics) of Zika virus infections in nonhuman primates have been documented.

Where monkey reservoirs of Zika virus are present, humans may be infected with virus transmitted from a monkey. When non-human primates are absent, as on Yap Island, where an outbreak occurred in 2007, mosquitoes transmit the virus from human to human.

The Zika virus outbreak in Brazil has been thought to have been mainly transmitted between humans by mosquitoes. However, the results of this new study suggests that nonhuman primates could also be involved. The authors used polymerase chain reaction (PCR) to detect Zika virus RNA in sera or oral swabs from 15 marmosets and 9 capuchin monkeys in Ceará State where the virus is currently circulating. Four marmosets and three capuchins tested positive for Zika virus in this test.

Nucleotide sequence analysis of the PCR products from one marmoset and one capuchin monkey showed 100% identity with the strain of Zika virus that is circulating in Brazil.

The sampled animals were obtained from distant regions of the State. The marmosets were all free-ranging but had contact with humans, while 8 capuchins were pets and one was kept in a screening center for wild animals.

If these findings are confirmed and extended to other parts of Brazil, they would suggest that Zika virus might be spreading through non-human primates in that country. If so, they could serve as a reservoir for infection of humans via mosquito vectors.

An interesting question is when Zika virus entered monkeys in Brazil. It has been suggested that the virus entered Brazil in 2013 or 2014, and might have spread first in monkeys, first in humans, or both at the same time. I also wonder whether monkey to human transmission leads to a different disease than when virus circulates among humans.

Zika virus comics: Zanzare

Dr. Susan Nasif is a virologist and part of the team at Cimaza Comics that produces science-themed comics. In their latest creation, Zanzare, we are plunged head-first into the global mystery of Zika virus. We meet the mosquitoes (in Italian: zanzare) implicated in its spread; but the insects plead their innocence, saying it’s all a misunderstanding. They lay their case before the gods and demons of Zika’s victims, and ask for divine help. Will the mosquitoes be vindicated? Or will it all turn out that the zanzare are to blame after all?

Not even the authors know where Zanzare is heading. The comics follow weekly developments in the Zika investigation as it unfolds. The story is told through the lens of world mythology, but the virology presented comes straight from reputable journals. Thrilling and funny, Zanzare is a visionary mixture of ancient legend and up-to-the-minute fact.

The video below is an excerpt from this series, which is not yet released in book form. Their previous creation, Adventures of the Regatjes, is available here.

TWiV 383: A zillion Zika papers and a Brazilian

TWiVEsper Kallas and the Merry TWiXters analyze the latest data on Zika virus and microcephaly in Brazil, and discuss publications on a mouse model for disease, infection of a fetus, mosquito vector competence, and the cryo-EM structure of the virus particle. All on episode #383 of the science show This Week in Virology.

Audio and full show notes for TWiV #383 at microbe.tv/twiv or listen below.

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Congenital Zika Syndrome

FlavivirusData from several clinical studies in Brazil establish a strong link between infection of pregnant women with Zika virus and a variety of birth defects collectively called congenital Zika syndrome.

In the latest study conducted in Rio de Janeiro, the authors enrolled 88 pregnant women who had a rash in the previous 5 days. Of the 88 subjects, 72 tested positive for Zika virus by PCR. Fetal ultrasound was performed in 42 of the Zika virus positive women, and in all the Zika virus negative women.

The results are convincing: fetal abnormalities were detected in 12 of the 42 Zika virus positive women (29%) and in none of the Zika virus negative women.

The abnormalities include fetal death (2), microcephaly (5), ventricular calcification or other central nervous system lesions (7), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7). These observations show that Zika virus infection may lead to birth defects other than microcephaly.

The infections of these pregnant women with Zika virus took place throughout pregnancy, from week 8 to week 35. This window of susceptibility is in contrast to rubella virus which is more likely to cause birth defects when infection occurs in the first trimester.

Not all Zika virus infections seem to cause birth defects – 29% in this study. If this number holds outside of Rio de Janeiro, then birth defects should also be observed in other countries with high rates of infection. Only 20% of Zika virus infections are symptomatic, and it will be important to determine if these also lead to congenital Zika syndrome.

The increase in microcephaly associated with Zika virus infection was first noted in the northeast of Brazil. This study was done with women who live in Rio de Janeiro, in the southeast of Brazil, showing that the association is not geographically limited.

It has been suggested that fetal defects might be partly due to the presence of antibodies to dengue virus that cross-react with Zika virus and cause immune-mediated enhancement of disease. Thirty-one percent of the Zika virus positive women in this study were also positive for antibodies to dengue virus, but the paper does not report how these correlate with fetal defects.

These findings, together with results of previous studies showing recovery of the entire Zika virus genome from amniotic fluid or from fetal brain, demonstrate that this fast spreading and newly emerging virus infection is clearly a threat to the developing fetus.

We should not be surprised that a virus that had until recently only infected several thousand individuals, and which we believed caused a mild, self-limiting rash, suddenly is found to be extremely dangerous to the developing fetus. The potential for fetal damage was likely always present, but unobserved until the virus was introduced into a large population of susceptible individuals and hundreds of thousands of individuals were infected. The lesson to be learned, often easily forgotten, is that we should always expect more from viruses than we initially observe. Such was certainly the case for HIV-1; immunodeficiency was only the tip of the clinical syndrome caused by infection.

Given the pace at which Zika virus is racing through susceptible humans, it is likely to generate enough population immunity in the next five years to curtail this outbreak. However as susceptible individuals are born and accumulate, regular outbreaks will likely occur. Similarly, outbreaks of rubella virus in the US occurred every 5-6 years in the pre-vaccine era.

Not only do rubella and Zika viruses cause similar fetal and placental abnormalities, in the mother they both lead to rash, joint pain, skin itching, and lymphadenopathy without high fever.

Hopefully the similarities between rubella virus and Zika virus will stop there: it took nearly 30 years to develop a rubella virus vaccine after the discovery that infection caused birth defects.

 

TWiV 378: Herpes plays DUBstep

TWiVOn episode #378 of the science show This Week in Virology, Greg Smith joins the TWiVirate to reveal how his lab discovered a switch that controls herpesvirus neuroinvasion, and then we visit the week’s news about Zika virus.

You can find TWiV #378 at microbe.tv/twiv, or you may listen below.

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TWiV 376: The flavi of the week is Zika

TWiVOn episode #376 of the science show This Week in Virology, the TWiV team discusses the latest data on Zika virus, including ocular defects in infants with microcephaly, and isolation of the entire viral genome from fetal brain tissue.

You can find TWiV #376 at microbe.tv/twiv.

Zika virus and microcephaly

FlavivirusThree reports have been published that together make a compelling case that Zika virus is causing microcephaly in Brazil.

An epidemic of Zika virus infection began in Brazil in April 2015, and by the end of the year the virus had spread through 19 states, many in the northeastern part of the country. Six months after the start of the outbreak, there was a surge in the number of infants born with microcephaly. It was not known if most of the mothers had been infected with Zika virus, as results of serological tests, virus isolation, or PCR were not available.

An initial report of 35 Brazilian infants with microcephaly born to women who either resided in or traveled to areas where Zika virus is circulating revealed that 74% of mothers had a rash (one sign of Zika virus infection) in the first or second trimester. At the time of this study no laboratory confirmation of Zika infection was available, but the infants did not have other infections associated with birth defects, including syphilis, toxoplasmosis, rubella, cytomegalovirus or herpes simplex virus.

Yesterday the CDC reported on the analysis of tissues from two infants with microcephaly who died within 20 hours of birth, and two miscarriages, all from the state of Rio Grande do Norte in Brazil. The mothers all had rashes typical of Zika virus infection in the first trimester of pregnancy, but were not tested for infection.

All four specimens were positive for Zika virus RNA by polymerase chain reaction (PCR) done with primers from two different regions of the viral RNA. Staining of tissues with anti-viral antibodies revealed the presence of viral antigens in two of the four samples, in the brain of one newborn and in the placenta from one of the miscarriages.

A second report from the University of Sao Paulo documents ocular abnormalities in Brazilian infants (from the state of Bahia) with microcephaly and presumed Zika virus infection. The mothers of 23 of 29 infants (79.3%) with microcephaly reported signs of Zika virus infection (rash, fever, joint pain, headache, itch, malaise). Of these, 18 (78.3%) had symptoms during the first trimester of pregnancy, 4 (17.4%) during the second trimester, and 1 (4.3%) during the third trimester.

No laboratory results were available to confirm Zika virus infections, but toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and HIV were ruled out.

Abnormalities of the eye were found in 10 of 29 (34.5%) of infants with microcephaly. These included focal pigment mottling, chorioretinal atrophy, optic nerve abnormalities, displacement of the lens, or a hole in the iris.

These observations suggest that Zika virus infection may also cause lesions of the eye, although confirmation of infection needs to be done to prove causation. This uncertainty is reflected in the title of the article: “Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil” (italics mine).

The final paper is, in my opinion, the blockbuster. In this single case report, a 25 year old European woman working in Natal, Brazil, became pregnant in February 2015. In the 13th week of gestation she had fever, muscle and eye pain, and rash. Ultrasound in Slovenia at 14 and 20 weeks revealed a normal fetus.

At 28 weeks of gestation fetal abnormalities were detected, including microcephaly, and the pregnancy was aborted. Autopsy revealed severe brain defects, and 42 to 54 nm virus particles were detected in the brain by electron microscopy.

Infection with a variety of microbes was ruled out, but Zika virus RNA was subsequently detected in brain tissue by PCR.

Here is the clincher – the entire Zika virus genome was identified in brain tissue by next-generation sequencing! Analysis of the sequence revealed 99.7% nucleotide identity with a Zika virus strain isolated from a patient from French Polynesia in 2013, and a strain from Sao Paulo from 2015. These findings agree with the hypothesis that the current Brazilian outbreak was triggered by a virus from Asia.

Up to now there have been few data that strongly link Zika virus infection to congenital birth defects. Of these three new studies, the recovery of a full length Zika virus genome from an infant with microcephaly is the most convincing. Given the rapidity by which new data are emerging, it seems likely that additional evidence demonstrating that Zika virus can cause microcephaly will soon be forthcoming.

I’m amazed that a flavivirus can cause birth defects – when no flavivirus has done so before*. This is a virus spread by mosquitoes, and to which most of the world is not immune. The Zika virus outbreak will surely test our ability to respond rapidly with substantial mosquito control, diagnostics, antivirals, and a vaccine.

Update 2/11/16: A second paper has been published documenting ocular abnormalities in ten infants born to mothers in Brazil who had symptoms consistent with Zika virus infection.

Update 2/12/16: *Japanese encephalitis virus and West Nile virus have been shown to cross the placenta and infect the fetus. Such events must be rare because a larger association with birth defects has not been reported.

TWiV 375: Zika and you will find

TWiVOn episode #375 of the science show This Week in Virology, the TWiVziks present everything you want to know about Zika virus, including association of infection with microcephaly and Guillain-Barré syndrome, transmission, epidemiology, and much more.

You can find TWiV #375 at microbe.tv/twiv.