The World Health Organization has declared the ongoing Zika virus outbreak a ‘Public Health Emergency of International Concern’. Spread of the virus has been linked to increases in the occurrence of the birth defect microcephaly and the neurological disorder Guillain–Barré syndrome. Though a causal relationship is yet to be established, health officials consider the evidence to be strongly suggestive. GENeS reached out to experts to find out how viruses like Zika may cause birth defects and Guillain–Barré syndrome.
Dr. Yoel Sadovsky, Director, Magee-Womens Research Institute, Elsie Hilliard Hillman Chair of Women’s Health Research, Professor of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh (webpage):
Expertise: maternal fetal medicine, mechanisms underlying placental development and dysfunction
“We know very little about how Zika virus infection occurs during pregnancy and how it causes birth defects. However, what we do know from other viral infections during pregnancy is that there are several steps that are needed for viruses to affect the fetus. The first is to get into the mother’s body and then to infect or cross the placenta. At that point, the virus can enter a specific fetal compartment such as neurons which could potentially lead to a defect such as microcephaly. Alternatively the virus can remain in the placenta and may affect development of the fetus by disrupting placental function.
“We know that the virus can get into the mother’s body through blood, airborne pathways or other means. In the case of Zika the mosquito bite transmits the virus into the mother’s blood. Once in the blood, the virus may potentially get through the placenta or infect cells which will carry the virus across the placenta. This is how cytomegalovirus which also causes birth defects, works.
“There is one other mechanism through which a virus could infect the fetus known as ‘ascending infection.’ In this case if a virus is present in the vagina, during the delivery process or after a rupture of membranes the virus can infect the baby within the birth canal. This has is believed to occur in HIV infection. However, this seems unlikely for Zika.
“It is possible that Zika infection causes birth defects during the first trimester, as many of the steps involving organ development are early pregnancy events. This is especially true for heart and brain development. Infection during the third trimester may be less likely to affect the fetus because many of the organs are already developed. It is also possible that the placenta is more competent to withstand infection in the third trimester.
“Apart from epidemiological findings and detecting the virus in the mother’s blood and in the fetus, an expert will need to examine brain tissues in children with microcephaly who were infected but did not survive. Identifying the virus in affected neurons would provide an extremely strong associative link suggesting that Zika could cause microcephaly.”
Dr. Alyssa Stephenson-Famy, Assistant Professor, Department of Obstetrics and Gynecology, University of Washington (website):
Expertise: maternal fetal medicine, maternal medical disorders in pregnancy
“Maternal infection either by a parasite, virus or bacteria eventually leads to the infectious agent entering the blood which can then infect the organs. Placental infection (which may persist even after the virus is cleared from the maternal blood and other organs) can either lead to spread of the virus to the fetal blood circulation or to the amniotic fluid surrounding the fetus which can then lead to fetal infection. Subsequently, the virus probably has certain fetal tissues that it may preferentially infect and destroy. For example the cytomegalovirus infects brain and digestive tract, parvovirus infects the bone marrow and rubella infects lens tissies leading to cataracts, etc.
“Zika is an interesting issue for us in maternal fetal medicine, because we have a few classic viral infections, like cytomegalovirus (CMV) which cause microcephaly and birth defects. CMV can be devastating to babies and fetuses but fortunately there is a relatively high rate of CMV immunity in the reproductive aged female population so primary acquisition of CMV in pregnancy is uncommon. What worries me about Zika virus is that it appears to cause similar growth issues, microcephaly and potentially other congenital issues, but in a population who has not been exposed to Zika virus and has no immunity. Globally mosquito born illnesses are either common (such as malaria) or rare (such as dengue) but with totally variable capacity to cause maternal illnesses, pregnancy complications or infect the placenta. I am not sure we have a good paradigm to use when thinking about Zika virus for this reason. Other than advising pregnant women not to travel to Zika reported areas and to look for evidence of microcephaly if they have visited one of these countries, we don’t have any robust ways to deal with this current epidemic as there is no vaccine or treatment available.”
Dr. Sasha Zivkovic, Associate Professor of Neurology, University of Pittsburgh Medical Center (webpage):
Expertise: Neuromuscular diseases; peripheral neuropathy; amyotrophic lateral sclerosis; neurologic complications of organ transplantation.
“Guillain–Barré syndrome is a potentially life-threatening autoimmune disorder where the body’s own immune system attacks peripheral nerves (nerves outside the brain and spinal cord). It manifests as rapidly progressive, symmetrical weakness of the limbs. Guillain–Barré syndrome may result in a significant disability and affects 1-2 per 100,000 in the population annually with a mortality of 5%. Preceding trigger events like infections or immunizations have been described in two-thirds of affected patients. Various infections can trigger Guillain–Barré syndrome including influenza, cytomegalovirus, Epstein-Barr virus and bacteria Campylobacter jejuni.
“The exact mechanism of an autoimmune reaction targeting peripheral nerves following an infection is not completely understood but it probably involves a molecular mimicry where the body’s immune reaction to bacteria or viruses may falsely recognize peripheral nerves as their target due to molecular similarity of the infectious agent with different components of peripheral nerves. Recent reports show that an infection with Zika virus may also precede Guillain–Barré syndrome, and initial studies from French Polynesia suggest that there may be an increased risk of Guillain-Barre syndrome when compared to other viral infections. There are ongoing studies in Brazil and French Polynesia trying to characterize the risk of post-Zika Guillain–Barré syndrome. The underlying mechanisms are still unclear and being investigated, but we can presume that it is similar to molecular mimicry described with other viruses that can trigger Guillain–Barré syndrome.”
Declared interests (see GENeS register of interests policy):
No interests declared