Zika Virus Threatens Both Adult and Fetal Brain Cells.
How Many Mosquito Species Can Spread Zika?
© 2016 by Linda Moulton Howe
“Zika can clearly enter the brain of adults and can wreak havoc.
But it's catastrophic for early brain development.”
- Sujan Shresta, Ph.D., La Jolla Inst. of Allergy & Immunology, Calif.
 
Left: Aedes aegypti ranges throughout all the southern tier of states in America.
Right: Aedes albopictus also ranges throughout all the southern tier states,
but goes as far north as Vermont and Minnesota. Images by CDC.
The New York Times, August 21, 2016.
August 26, 2016 Penn State, University Park, Pennsylvania - The 2016 Olympic Summer games in Rio de Janeiro, Brazil, are over, but the worries about rapidly spreading Zika virus infections from Brazil throughout the Americas, including the United States, are growing. For the past few months, we have heard about the Zika virus causing the small, damaged brain syndrome known as microcephaly in pregnant women. The virus gets into people from mosquito bites. Zika can travel from its puncture into human flesh to a pregnant woman's placenta and move through blood into developing foetuses.
Sophia, 2 weeks old, was born in Brazil with
microcephaly, a victim of the Zika virus that attacked her
fetal brain cells. Image © by Felipe Dana/AP.
Microcephaly cases in Brazil, the rest of South America, Central America, Mexico, Haiti and Puerto Rico are now estimated to be in the thousands. Puerto Rico alone has over 13,000 confirmed Zika infections. Some have caused microcephaly, but now adults are also suffering nerve damage. 34 Puerto Rico adults with Zika infections have developed Guillain-Barre syndrome, which causes weak muscles and can paralyze. Two Puerto Rican men so far have died from Guillain-Barre paralysis in August and April.
Associated Press report on NBC News, August 19, 2016.
This means that Zika is not only attacking and destroying developing fetal brain cells, but can damage brain tissues in adult men and women.
Original 1947 Mild Zika
Has Mutated to Growing Threat
Since its first discovery in monkeys living in the Zika Forest of Uganda in 1947, the Zika virus was not known to mutate. In sixty years from 1947 to 2007, only 14 cases of Zika infection in humans had been reported. Small outbreaks in Africa and later in Southeast Asia were mild with a rash that soon went away. Zika was never associated with birth defects or adult paralysis.
But by 2007 to 2008, something began changing in the Zika virus when there was a large outbreak in Yap, Micronesia, and a U. S. scientist working in Senegal was infected with Zika, returned home to Colorado and infected his wife in what is probably the first documented case of sexual transmission from human sperm.
Zika Virus Is Spread by Mosquitoes
Human Zika virus infection has mutated in character while expanding its geographical range throughout the Americas and is attacking progenitor brain cells in both developing foetuses and adults. There are 3,500 species of mosquitoes known throughout the world and the biggest Zika virus carriers so far are are Aedes aegypti and Aedes albopictus:
Aedes aegypti.
Aedes aegypti that lives in at least 24 states from Connecticut to Florida across the southern tier to California and bites humans. On August 16th, New Mexico Senator Martin Heinrich announced the creation of a Zika Resource Center because four cases of Zika in New Mexico where the Aedes aegypti mosquitoes live have already been confirmed in people who traveled. Mosquitoes can pass Zika from those infected people from more bites. It's also confirmed that male sperm can carry the live Zika virus for a couple of weeks and infect sexual partners that could include impregnation of an unsuspecting female, who could then carry a foetus with microcephalic brain damage.
Aedes albopictus.
A second mosquito carrier of Zika are the Aedes albopictus — which bite animals and birds in addition to humans. This mosquito’s range is even bigger through the entire eastern half of the United States, plus New Mexico, Arizona and California.
Culex pipiens.
A third possible mosquito carrier of the Zika virus is Culex pipiens and it is found everywhere in the United States.
How Mosquitoes Transmit Zika Virus
Diagram credit: The Anatomical Life of the Mosquito by R. E. Snodgrass.
One scientist at Penn State in University Park, Pennsylvania, likes to study mosquitoes and this month was awarded a 2-year-grant from the National Institutes of Health to search for Zika virus in mosquito guts and salivary glands that can enter humans through bites. He is Jason Rasgon, Ph.D., Associate Professor of Entomology and Disease Epidemiology.
Interview:
Jason L. Rasgon, Ph.D., Assoc. Prof.
of Entomology and Disease Epidemiology,
Penn State College of Agricultural Sciences,
Dept. of Entomology, University Park, PA.
Jason L. Rasgon, Ph.D., Assoc. Prof. of Entomology and Disease Epidemiology, Penn State, University Park, Pennsylvania: “This outbreak (in Brazil) was very different from everything that’s happened in the previous 60 years. It (Zika outbreak in Brazil) was much larger and it’s still going on obviously. And so for the first time, we were seeing Zika virus infection being associated with Guillain-Barre syndrome, which is an autoimmune disorder that is triggered by an infection, which causes paralysis. And there’s no real treatment for it. It goes away, but if you don’t get to a hospital, it can paralyze your breathing apparatus (lungs and diaphragm) and you can’t breathe and you die.
PROFESSOR RASGON, LET ME MAKE SURE I UNDERSTAND. SUDDENLY, IN 2015, CENTERED AROUND SALVADORE, BRAZIL, ZIKA IS SPREADING TO ADULTS AND CAUSING THE GUILLANE BARRE SYNDROME OF PARALYSIS IN ADULTS?
Yes, and then we saw the fetal birth defects — the microencephaly and everything else. That’s never been seen before. And so definitely, I think it is 100% clear that Zika is associated and is a factor in newborn microencephaly and neurological birth defects.
What is not clear is Zike the only thing responsible? Because the data here are very new. When you look at the outbreak that is happening in Colombia right now. We are not seeing newborn microcephaly — not nearly to the extent that we’re seeing it in Brazil. So there could be other confounding factors where the Zika virus infection is one of the factors, but it has to be in conjunction with something else. And what that something else is, we don’t really understand yet.
Mutating Zika Virus
WHAT DO YOU THINK HAS CHANGED SUDDENLY BETWEEN YAP (MICRONESIA 2007 ZIKA OUTBREAK) AND SALVADOR, (STATE OF BAHIA) BRAZIL, AND NOW SPREADING TO COLOMBIA, THE UNITED STATES AND PERHAPS AROUND THE WORLD?
So, it could be the birth defects that we’re seeing now that we didn’t see then — the first explanation is that the Zika virus mutated. And now it’s causing problems. So, there has been some data to suggest that the virus is genetically different. Another explanation is the size of the outbreak. So all of a sudden you have a million people infected, you’re seeing those negative outcomes occurring.
HOW MANY WOMEN RIGHT NOW HAVE BEEN IDENTIFIED IN BRAZIL OR COLOMBIA, WHO HAVE HAD BIRTHS WITH MICROCEPHALY?
Going to be thousands! If Zika was not causing fetal birth defects — even if this outbreak were huge the way it is — nobody would care. Males should be concerned because if they are infected, they can transmit the virus sexually to their partner. Then you would potentially see the complications with fetal birth defects.
Sexual Transmission of Zika Virus in Sperm
BUT WHAT IS SO INSIDIOUS NOW ABOUT THE ZIKA VIRUS IS THAT THE TRANSMISSION CAN BE THROUGH SEXUAL INTERCOURSE BEFORE EITHER PARTNER KNOWS WHAT HAS HAPPENED AND THEN IF THERE IS A PREGNANCY …
Yes.
… THERE IS A LIKELIHOOD, BASED ON THE BRAZIL DATA, THAT THERE COULD BE MICROENCEPHALY, THE SMALL HEAD SYNDROME AND BRAIN DAMAGE.
Yeah, in Zika, about 4 out of 5 people who get it, don’t have any symptoms. That doesn’t mean it’s not having affect on the foetus.
YES.
The sexual transmission thing is very interesting because we really haven’t seen that before.
WHEN IS THE WOMAN WITH THE DEVELOPING FOETUS THE MOST VULNERABLE TO GETTING THE MICROCEPHALY IN THE FOETUS?
What we know now is that the earlier a woman gets infected, the worse it’s going to potentially be for the foetus. But, there have been documented cases where the infection at any stage in the pregnancy can be harmful. And particularly if a woman gets infected before she knows she is actually pregnant. That first trimester seems to be the case where the worst fetal birth defects are seen. And that makes sense because that’s when the nervous system is actually beginning to develop.
THIS IS A VIRUS THAT IS ATTACKING THE NERVOUS SYSTEM IN THE DEVELOPING FOETUS.
Yes.
ANY IDEA AT THIS POINT WHY THAT WOULD BE FROM THE ZIKA VIRUS?
I have no idea. I don’t know epidemiologically and I don’t know molecularly. There are people who are trying to work that out. But there have been studies to show that growing balls of brain cells in a dish, the virus seems to have unusual tropism for the foetal nervous tissue cells. [ Tropism is the turning of all or part of an organism in a particular direction in response to an external stimulus.]
And it (Zika virus) can also cross the placenta, so it can go from the mother to the foetus.
THAT’S UNUSUAL IN AND OF ITSELF, ISN’T IT?
I think it’s relatively unusual, yes.
Penn State Mosquito Research
WHAT ARE YOU NOW GOING TO DO IN YOUR RESEARCH AT PENN STATE?
I’m interested in looking at — particularly in North America — what mosquitoes are competent to transmit the Zika virus. So we already know that Aedes aegypti and Aedes albopictus are competent to transmit. Those are considered to be the vectors that are responsible for transmitting virus.
When people were talking about the risk of Zika introduction into the United States, all of the estimates of risk are based on the assumption that Aedes aegypti and Aedes albopictus are the only mosquitoes that can actually transmit Zika virus.
We don’t actually know. So, if some other mosquito in the U. S. such as Culex pipiens, or something else, is competent to transmit virus. Then everything that we’re saying about the ris of introduction needs to be re-evaluated.
[ Editor’s Note: Culexis a genus of mosquitoes, several species of which serve as vectors of one or more important diseases of birds, humans and other animals. The diseases they vector include arbovirus infections, West Nile virus, filariasis, Japanese encephalitis, St. Louis encephalitis, and avian malaria.]
WHEN YOU SAY COMPETENT TO TRANSMIT, CAN YOU EXPLAIN WHAT THAT MEANS?
Yeah. So, we take the mosquitoes in the laboratory and we have an artificial blood feeder that we spike with the Zika virus. And then we assess can the virus infect the mosquito gut? Can it get out of the mosquito gut and infect the other mosquito tissues?
And then can it infect the mosquito salivary glands and be secreted into the saliva and be secreted by a mosquito when it’s biting?
So, we have been looking for infectious virus in the mosquito saliva. If we can find that, then we say, ‘Yes, this mosquito is competent to transmit Zika virus.
HOW MANY SPECIES OF MOSQUITOES ARE THERE AROUND THE WORLD?
There is about 3,500 species of mosquitoes.
IF ALL OF THEM ENDED UP BEING ABLE TO TRANSMIT THE ZIKA VIRUS, WE COULD HAVE A REALLY SERIOUS GLOBAL PROBLEM WHEN IT COMES TO PREGNANCIES.
Yeah. Zika has actually been isolated from mosquitoes in the field from 26 different species of mosquitoes. Now, just because you isolate virus from mosquitoes in the wild does not mean it transmits it. Because you can have a virus that’s able to infect the mosquito’s guts, but it never gets out of the gut — can’t get to the salivary gland, so the mosquito can’t transmit the virus.
But it suggests that more than these two species are capable [Aedes aegypti and Aedes albopictus.] It’s not going to be all of them, but even if one other — say Culex pipiens, which is a widespread mosquito. Or Culex quiinquefasciatus.
Culex quiinquefasciatus.
[ Editor’s Note: Culex quinquefasciatus (earlier known as Culex fatigans), the southern house mosquito, is a medium-sized mosquito found in tropical and subtropical regions of the world. It is taxonomically regarded as a member of the Culex pipiens species complex. Its genome was sequenced in 2010, and was shown to have 18,883 protein-coding genes.]
The potential range of Zika risk is going to be greatly expanded. We’re not talking about all mosquitoes, but it doesn’t have to be all mosquitoes — just another couple ones, depending on what they are, could have a large affect on our estimates of risk.
Could Zika Become A Pandemic?
HAVE YOU TALKED WITH SOMEBODY AT A POLITICAL GOVERNMENT LEVEL NOW AS SOMEBODY WHO KNOWS A GREAT DEAL ABOUT MOSQUITOES — THAT THIS COULD BECOME A KIND OF PANDEMIC?
Yeah. I don’t like to throw around words like ‘pandemic.’ We have viruses and things that are transmitted like West Nile, which has moved around the world. And I’ve talked to some of the state governmental officials here in Pennsylvania. They came and asked me.
Then we have to talk about the behavior of the mosquitoes. You can have mosquitoes that are biologically competent to transmit a pathogen. But they don’t feed on people. They always feed on cows and people or whatever.
Aedes aegypti is a better vector because it really only feeds on people. The Zika virus can only replicate in people. Aedes aegypti feeds only on people, so their transmission efficiency is kind of amplified.
If a pregnant woman is infected, there is nothing she can do to protect her foetus at that point. Whatever is going to happen is going to happen.
RIGHT, AND RIGHT NOW THE WORST CASE IS THAT WE DID NOT KNOW ENOUGH IN THE LAST TWO MONTHS TO PROTECT PEOPLE, WHO HAVE BECOME PREGNANT — NOT JUST IN BRAZIL.
Yeah, everywhere! Puerto Rico has been having a raging outbreak since February. They’ve had 1,500 cases. They’ve had about almost 200 pregnant women that have been infected. Nobody cares about Puerto Rico! They only start caring when 14 people get infected in Florida.
Millions of Zika Cases
in Brazil and South America
AND BRAZIL — TALK ABOUT HOW BIG THE PROBLEM IS IN BRAZIL AND SOUTH AMERICA.
Millions of cases!
MILLIONS?
Yeah, millions! It’s a huge outbreak.
ARE WE NOW TALKING ABOUT THE POSSIBILITY THAT WHAT EVER IS HAPPENING WITH THE ZIKA VIRUS IS READY TO SPRING IN OTHER PARTS OF THE WORLD?
I don’t know. I look at the epidemiological consequences of Brazil versus Colombia. We’re not seeing the same magnitude of affects that we’re seeing in Brazil. So we don’t really know if Zika is the only thing responsible for these things. Or is there some other confounding factor. I think those confounding factors are going to be important. Zika is going to spread around!
IF THE VIRUS HAS MUTATED, IS THAT MUTATION SOMETHING THAT IS NOW GOING TO CONTINUE TO BE AN INCREASING PROBLEM? AND HOW WILL YOU KNOW EXACTLY WHAT THE GENETIC SEQUENCING IS THAT MIGHT BE CAUSING THE PROBLEM?
We don’t know if those mutations are responsible for making it worse. So, we have several different viral isolates, including the original 1949 isolate from Uganda. And then we have three or four different isolates that are from the outbreak in Nicaragua, Colombia and Brazil. We’re testing the historic isolate with the (modern) outbreak isolates. Can they infect novel mosquito vectors that are present in the United States? Do they transmit? Or do they not transmit?
DO YOU THINK THERE IS A POTENTIAL THAT THIS COULD SPREAD TO THE OTHER PARTS OF THE WORLD …
Yes.
… LET’S SAY, OVER THE NEXT FEW MONTHS?
Probably not in the next few months, but I would be very interested to see what happens here, especially now that we’re looking for it.
WHAT IF FLORIDA LOSES CONTROL ON THE MOSQUITO IMPACT ON THE POPULATION AND THAT WE END UP WITH A THOUSAND CASES OF MICROENCEPHALY IN FLORIDA —AND SPREADING ?
Well, I think the Governor, Rick Scott, needs to stop saying irresponsible things in the media about how the Zika control area has shrunk. (It has not.) I think that was incredibly irresponsible! (laughs ironically)
THEY ARE WORRIED ABOUT TOURISM.
Yeah, they are worried about tourism! (laughs ironically) I think if we have a major outbreak of microencephalic babies being born in Florida from local transmission, they are going to drench the state with insecticides, which is what I would recommend. Do everything you can to avoid being bitten by a mosquito.”
Adult Mice Study of Zika Virus
Journal of Cell Stem Cell, August 8, 2016: Study of adult mouse brains at Rockefeller
University and La Jolla Inst. for Allergy and Immunology.“ (B and C) Adult TKO mice were
infected with ZIKV (Zika virus) and then sacrificed, their brains were serially sectioned,
and they were immunostained for ZIKV envelope protein (green). Evidence of ZIKV
was found in the subventricular zone, SVZ, and subgranular zone, SGZ, with less
expression elsewhere in adult brain. High-power inset below with arrows (yellow)
highlights immunoreactive cells. LV, lateral ventricle. Scale bar, 100 μm.”
On August 8th, the journal Cell Stem Cell published the first study to look at Zika virus infection on adult brains of mice at Rockefeller University and La Jolla Institute for Allergy and Immunology. Using fluorescent biomarker green stains to mark the Zika protein covering, the virus concentrated in neural progenitor cells that are supposed to keep making new brain neurons through life. To lose progenitor cells means reduced brain volume and that means difficulty remembering and learning.
So Zika attacking and destroying neural progenitor cells in foetuses, especially in the first three months when brains are forming, would explain why Zika causes smaller-than-normal heads and developmental disabilities in newborns. This new research might also explain why some human adults suffering the Guillain-Barre syndrome that can cause paralysis.
Louisiana Floods Increase
Zika Infection Danger
Before the week-long heavy rains of August 9 to 16, flooded an estimated 140,000 homes in metropolitan Baton Rouge, Louisiana, and more homes southwest in Lafayette, U. S. health authorities thought the Zika virus could be contained in Florida. But now all that receding flood water is the perfect place for mosquitoes to live and bite humans.
Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, said this week, “I would not be surprised if we now see Zika cases in Texas and Louisiana. There are going to be a lot of problems getting rid of standing water.”
On top of that, Miami-Dade County’s Wynwood and Miami Beach regions are the first U. S. mainland places to report Zika infections in people who have not traveled. That means local Florida mosquitoes are carrying and transmitting the Zika virus from their bites. Pregnant women in Florida have been advised to not visit the active Zika zone in Miami Beach and to stay in doors as much as possible.
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