West Nile virus causes fetal brain damage like Zika

West Nile and Powassan can spread from an infected pregnant mouse to her fetuses, causing brain damage and fetal death, according to a new study from Washington University School of Medicine in St. Louis. The findings suggest that Zika may not be unique in its ability to cause miscarriages and birth defects.

It is possible that viruses related to Zika, such as West Nile, pose the same risk to developing fetuses that Zika does. Researchers linked Zika infection in pregnant women with the risk of bearing babies born with microcephaly, or abnormally small heads.

Like Zika, both belong to the flavivirus family and target neural tissues. West Nile Virus (WNV) has the potential to cross the placenta and damage developing fetuses, according to new studies in mice. As part of the study and for comparison, Platt and Miner also wanted to study the effects of two mosquito-borne viruses only distantly related to Zika: chikungunya and Mayaro. Both are found in Brazil and can cause arthritis.

They injected female mice at day six of their pregnancies with one of the four viruses, then examined the placentas and fetuses a week later. All four viruses infected the placentas and fetuses, but levels of West Nile virus were 23- to 1,500-fold higher than those of the other three viruses in the placentas, and 3,000- to 16,000-fold higher in the heads of the fetal mice.

In addition, brain tissue from West Nile-infected fetuses showed severe damage under the microscope, while brain tissue from chikungunya-infected fetuses appeared healthy. They found that the three flaviviruses - Zika, West Nile and Powassan - multiplied in human placentas while chikungunya and Mayaro did not.
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Repurposed drug effective for Zika virus

In both cell cultures and mouse models, a drug used to treat Hepatitis C effectively protected and rescued neural cells infected by the Zika virus and blocked transmission of the virus to mouse fetuses. Researchers at University of California San Diego School of Medicine, with colleagues in Brazil and elsewhere, say their findings support further investigation of using the repurposed drug as a potential treatment for Zika-infected adults, including pregnant women.

 Zika infection during the first trimester confers the greatest risk of congenital microcephaly. Outbreaks of Zika virus in Brazil in 2015 and 2016 were marked by an increased incidence of newborns with congenital malformations, most notably undersized heads (microcephaly) and significant neurological abnormalities.

A great deal of research has focused on the pathology of Zika infections, including earlier work by the Muotri lab and collaborators that described how the virus is transmitted from mother to fetus by infecting cells that, ironically, will later develop into the brain's first and primary form of defense against invasive pathogens.

In its latest work, however, the Muotri lab sought clinical solutions. The team investigated an antiviral drug called sofosbuvir, approved and marketed under the brand name Sovaldi to treat and cure hepatitis C infections. The drug works by inhibiting replication of the hepatitis C virus; researchers noted that both hepatitis C and Zika belong to the same viral family and bore strong structural similarities that could make sofosbuvir effective against the latter. In addition, it had been reported that sofosbuvir was protective against Zika in different cell types.

In tests using human neural progenitor cells (NPCs)-self-renewing, multipotent cells that generate neurons and other brain cell types-the scientists found that exposure to sofosbuvir not only rescued dying NPCs infected with the Zika virus, but restored gene expression linked to their antiviral response. In subsequent tests using an immunodeficient mouse model infected by Zika, intravenous injections of sofosbuvir significantly reduced viral loads in blood serum compared to a placebo group.

Fetuses of Zika-infected pregnant mice did not show detectable Zika virus amplification in the sofosbuvir-treated group. This shows that the drug was well-tolerated by the Zika-infected pregnant mice and that it was able to arrest Zika replication in vivo and stop transmission from mother to fetus.
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Dengue immunity can protect against Zika

Manifestations of Zika virus (ZIKV) infection differ drastically. Sometimes they are catastrophic, most notably when they cause microcephaly in some babies born to infected mothers. At other times, they are mild and fleeting, suggesting that unknown factors temper Zika infections' severity.

Recently, dengue virus emerged as a prime suspect because it shares many genetic and structural characteristics with ZIKV and is endemic in most of the regions affected by Zika's global spread.
Mice rendered immune to dengue show "cross-protection" from subsequent Zika infection and then identifies specific types of immune T-cells capable of defending against both viruses.

These revelations have profound implications for efforts to build a potent anti-Zika vaccine. In some parts of the world Zika is almost like a secondary infection. It has spread into Brazil/Latin America and is moving into places in Asia where people previously had dengue. Vaccines targeting either virus could be engineered to induce both T cell and antibody responses effective to protect people in these areas.

When one encounters a pathogen in real life, two arms of the immune system spring into action to neutralize it. In the so-called humoral response, B-cells begin to secrete specific antibody proteins, which latch onto and neutralize pathogens in tissue or blood. Simultaneously, a cell-mediated immunity system also becomes active, deploying cytotoxic T-cells to directly recognize and kill pathogen-infected cells.

The ideal vaccine might mimic both antibody and T cell responses to block an infectious disease. But in truth, most (26 of 28 vaccines currently licensed for human use) stimulate primarily a B-cell or antibody response, which in many cases is sufficient. Reseache team created the first "sequential" mouse model mimicking dengue-then-Zika infection. To do that, they infected mice genetically vulnerable to this family of viruses with dengue virus.

Those mice became sick, recovered from infection, and hence acquired immunity to dengue, presumably because viral infection had mobilized their immune B-cells, T-cells or both. The group then inoculated the same mice with ZIKV and waited to see if mice showed ZIKV symptoms. But overall, mice that had previously acquired dengue immunity showed protection against Zika, as evidenced by a reduced burden of ZIKV in blood and tissues, such as brain, liver or testis, compared to control mice not "pre-inoculated" against dengue.

These experiments suggest that the reason that some people infected with Zika do not come down with disease is due to prior exposure to dengue. This may explain why Zika is not passed to the unborn child of every pregnant woman in dengue-endemic countries exposed to virus. In a different experiment, the scientists isolated cytotoxic T cells from the blood of dengue-immune mice and infused them into normal mice, a procedure known as adoptive T-cell transfer.

 When infused mice were then infected with ZIKV, they also showed disease resistance, supporting the idea that the T-cell arm of the immune system can do the heavy lifting against ZIKV infection. A successful vaccine would need to include components to induce not only a B-cell response but also a T-cell response.
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Potential Zika vaccine prevents pregnancy transmission and testicular damage

Zika infection typically results in mild or symptom-free infections in healthy individuals, infected pregnant women without symptoms may still give birth to a baby with birth defects like microcephaly.

Researchers has shown that a potential Zika vaccine can protect fetuses against infection and  protect males against testicular infection and injury. It also prevents a lowered sperm count after one vaccination.

Infected men without any signs of illness may still incur testicular injury and lowered sperm count. The Zika virus could infect the male reproductive system for several months, posing risk for sexual transmission.

Taking a single-dose vaccine could prevent Zika infection in non-human primates, prevent mother-to-fetus transmission, and stop male testis infection in mice. The vaccine provides a protective immune response, this vaccine exhibited an excellent safety profile in mouse and non-human primate models.
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Zika virus weakened immune system and deformed fetus

The Zika virus increases in pregnant women by suppressing their dampened immune systems and attacks their natural defenses, which allows the virus to directly attack the fetus. A woman's immune system naturally suppresses itself during pregnancy to keep the body from recognizing the fetus as a foreign body and attacking it, Zika uses this process, turning pregnant woman's immune defense so the virus can spread without any hindrance.

Researchers tested African and Asian strains of Zika in the blood samples of healthy men, women and pregnant women. Researchers discovered that the Asian strain of Zika targets monocytes, which are white blood cells that mount the body's immune defense by destroying viruses and bacteria, people can survive the attack, but pregnant women cannot because Zika exploits the existing process by which the body protects a fetus from immune attack. Zika virus suppresses immune system like HIV.

The virus goes in, multiplies, grows and then crosses the placenta attack the fetus and cause disease. The blood of pregnant women infected with Zika also showed abnormally high expression of two genes that have been previously associated with pregnancy complications. Microcephaly have been associated with mothers who were infected with the Zika virus before giving birth, a pregnant women naturally have higher levels of immune-suppressing M2 macrophages to prevent the womb from rejecting the fetus.

However, the Asian Zika virus boosts M2 macrophage reproduction, decreasing the infection fighting process and encouraging immune suppression. Researchers discovered that the Asian Zika virus is more dangerous during first and second trimester, when the virus can increase immune suppression. During the third trimester, the blood of infected pregnant women and non-pregnant women were about the same.

During pregnancy, the host body is prone to opportunistic infection
Previous clinical studies showed that Zika virus infection during the first and second trimesters of pregnancy are strongly associated with fetal abnormalities. These anomalies cause brain damage and developmental delays in babies even if they are born with normal-sized heads.
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Zika may not last in semen as thought

According to the latest research, Zika virus might not remain in the semen of some infected men as long as previously thought.

The researchers said Zika may only be present in semen for about a month. Previous research had suggested that Zika virus can be found in semen for as long as 188 days after the onset of symptoms.

The new study included 12 men in French Guiana who had Zika virus. Four of the men never had any detectable Zika in their semen. One excreted Zika virus in his semen for at least three days. And seven had Zika-laced semen for at least a month.

The maximum duration of detectable Zika in semen in the study was 45 days.
These data suggest that not all men who are symptomatically infected with Zika virus will have Zika virus RNA detectable in semen.

The results also showed that Zika does replicate in the testicles or semen-producing glands, since the amount of Zika in semen was significantly different than the Zika load found in the men's blood.

Zika causes neurological birth defects, most commonly microcephaly, a condition in which a baby's brain and skull are underdeveloped.
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Improved, safer Zika vaccine

Scientists have come up with better plant-based Zika vaccine that is more potent, safer and cheaper. It's based on key Zika protein. The vaccine works against a part of a Zika viral protein, called DIII, the part of the virus that infect people.

All flaviviruses have the envelope protein on the outside part of the virus. It has three domains. The domain III has a unique stretch of DNA for the Zika virus, this is used to generate a protective immune response that is unique for Zika.

Scientists carried out immunization experiments in mice, which induced antibody and cellular immune responses that have been shown to confer 100 percent protection against multiple Zika virus strains in a mouse.

The envelope protein were grew in bacteria, then switched to prepare the DIII protein domain in tobacco plants.
Producing plant-based vaccines, especially in tobacco plants, is safer than using chemical-based.

The protein-based vaccine uses the smallest and most unique part of the Zika virus that can still draw out a potent and good immune response.

Scientists made a pseudovirus- fake virus. The pseudovirus displays only the DIII part of the envelope protein on the surface. Making the full native envelope protein as the basis for a vaccine, it induced antibodies against DI, DII and the DIII domains of the protein.

Women were advised not to become pregnant because Zika virus can cause abnormalities in babies. It can cause
severe brain defect known as microcephaly, in which the head and brain don't develop properly.

It can also cause vision, hearing defects and learning disabilities associated with less severe infections. Gullian-Barre syndrome in adults  has also been linked to Zika virus.
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Gene mutation can leads to brain malformation

Gene controls nerve stem cell growth and how it causes abnormal brain development in fetuses if the system goes wrong. Researchers explained how Dmrta2 controls gene in the division of cells and the production of specialised cells.

If Dmrta2 gene mutation is inherited from parents, it can cause brain malformations known as lissencephaly. Lissencephaly is a nervous system disorder in which a baby's brain is not fully developed.

Lissencephaly occurs in the second trimester of pregnancy, and leaves the fetus with a small brain and it prevents the development of brain folds and grooves which are needed for language skills and learning.

Researchers genetically mutated the Dmrta2 gene in embryonic stem cells to check the impact of too much or too little protein levels on brain development.

 They examined the effect of these changes on laboratory-created nerve cells, it shows a direct link between Dmrta2 mutation and the microcephaly.

When Dmrta2 gene is not maintaining balance between neurogenesis and cell cycle progression, brain development is altered. This can cause neurodevelopmental condition like autism.
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Zika virus causes more diseases in children

Zika could be more dangerous to unborn babies because test on pregnant monkeys infected with the virus found that every single fetus had picked up some trace of Zika.

 The research team infected four pregnant rhesus macaque monkeys at the Wisconsin National Primate Research Center with a Zika virus and
discovered that the virus was present in each monkey's fetus.

The research group also found damage from Zika in every part of the interface between mother and fetus - the placenta, amniotic fluid in the womb and the lining of uterus.

Three of the baby monkeys were born with small heads, but not as small as it would need to be to meet the human standard for diagnosing microcephaly.

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Vaccine protects mice from Zika virus

New Zika vaccine was made from live virus that has been inactivate and it shows effectiveness in mice.

Producing a better vaccine will require a balance between efficacy and safety of the user, vaccine produced from attenuated live viruses normally offers fast immunity but not safe.

Inactivated and subunit viruses always provide safety but may required several initial doses, safe live-atteuation  vaccine will be used for production of Zika vaccine for human in developing countries.

Zika vaccine showed safety profile in mice, this vaccine will prevent transmission of the virus and microcephaly and prevent birth defects and diseases caused by Zika.

The vaccine will be recommended for women of child bearing age, their sexual partner and children less than 10 years.