Zika Birth Defects More Severe When Mothers Infected During First Trimester

MedicalResearch.com Interview with:

This image depicts a posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus. Note: Not all patients with Zika get a rash CDC image

This image depicts a posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus.
Note: Not all patients with Zika get a rash
CDC image

Professor Bruno Hoen, M.D., Ph.D
Dept of Infectious Diseases, Dermatology, and Internal Medicine
University Medical Center of Guadeloupe 

MedicalResearch.com: What is the background for this study?

Response: Zika virus (ZIKV) infection during pregnancy has been identified only recently to cause severe birth defects, including microcephaly, other brain defects, and the congenital Zika syndrome. However, the magnitude of this risk was not clearly defined, with discrepancies between observational data from Brazil and the U.S. Zika Pregnancy Registry. We implemented a cohort study of pregnant women who have been exposed to ZIKV throughout the outbreak that hit the Caribbean in 2016.
Continue reading

Autoantibodies Generated By Zika Virus May Explain Some Consequences of Infection

MedicalResearch.com Interview with:

Slobodan Paessler, D.V.M., Ph.D. Associate Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core;  Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch  Galveston, TX

Dr. Paessler

Slobodan Paessler, D.V.M., Ph.D.
Professor, Department of Pathology;
Director, Galveston National Laboratory Preclinical Studies Core;
Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity;
Member, Center for Biodefense & Emerging Infectious Diseases
University of Texas Medical Branch
Galveston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus infection is associated with various developmental issues for human embryos such as reduced head growth, reduced brain tissue growth, and damage to brain or eyes. We wanted to better understand if some of these birth defects are caused directly by the Zika virus or maybe by the host response to infection.

In our study we demonstrate that the Zika virus infection induces autoimmune response against the C1q protein. This protein is a very important immune protein as well as one of the essential proteins for healthy brain development. Attacking the C1q protein upon exposure with the Zika virus could contribute to the development of autoimmune disorders and birth defects.  Continue reading

Salivary Assay Developed for HIV Can Be Used To Detect Zika

MedicalResearch.com Interview with:

Researchers at NYU College of Dentistry are developing a test for Zika virus that uses saliva to identify diagnostic markers of the virus in a fraction of the time of current tests. NYU/Sapna Parikh

Researchers at NYU College of Dentistry are developing a test for Zika virus that uses saliva to identify diagnostic markers of the virus in a fraction of the time of current tests.
NYU/Sapna Parikh

Maite Sabalza Ph.D
Post Doctoral Associate
Department of Basic Science and Craniofacial Biology
College of Dentistry, New York University
New York, NY 10010

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: With previous NIH funding we were able to develop an automated “dual assay” (able to detect both host antibodies and viral RNA) for HIV.

In relatively short time, we were able to migrate those findings into the new assay for ZIKA Virus. Continue reading

ZIKA: Mouse Study Finds Antioxidant Ebselen Reduces Risk of Sexual Transmission

MedicalResearch.com Interview with:

Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth. Wikipedia image

Image of a baby with microcephaly (left) compared to a normal baby (right). This is one of the potential effects of Zika virus. Signs of microcephaly may develop a few months after birth.
Wikipedia image

Yogy Simanjuntak PhD
Postdoctoral Research Fellow
Institute of Biomedical Sciences
Academia Sinica, Taiwan 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite the low case fatality, Zika virus infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Primarily transmitted by Aedes species mosquitoes, Zika also can be sexually transmitted in humans. By August 2016, the sexual transmission of Zika had been documented in 11 countries worldwide and most of the cases were from male to female. Infectious Zika in semen has been reported. Moreover, unlike in serum or urine samples, Zika RNA can still be detected in semen up to 188 days after the onset of symptoms. In the absence of approved antiviral drugs or vaccines for Zika infection, preventing the disease transmission is critical.

We observed Zika progressively damaged testes by gaining access to testicular cells including sperm. Notably, Zika caused signs of increased testicular oxidative stress and inflammation, characterized by high levels of reactive oxygen species and pro-inflammatory cytokines. Our data indicate that these factors may contribute to testicular damage as well as successful sexual transmission of Zika; thus, we speculate antioxidants might display beneficial effects to alleviate these disease outcomes.

We found that antioxidant ebselen both alleviated testicular damage and prevented sexual transmission of Zika via sperm from infected male mice to uninfected female mice.

Continue reading

More Evidence for Zika as a Causal Agent Of Guillain-Barré Syndrome

MedicalResearch.com Interview with:

Emilio Dirlikov, PhD Epidemic Intelligence Service Officer CDC 

Dr. Dirlikov

Emilio Dirlikov, PhD
Epidemic Intelligence Service Officer
CDC 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In December 2015, Puerto Rico Department of Health (PRDH) reported its first confirmed locally acquired case of Zika virus disease. In February 2016, PRDH reported the first person diagnosed with Guillain-Barré syndrome (GBS) who also had evidence of Zika virus infection. At the time, scientific evidence of the potential association between Zika virus infection and GBS was lacking, and rigorous studies were needed.

Through a collaboration between PRDH, CDC, and the University of Puerto Rico (UPR), we conducted a case-control study to determine risk factors for GBS during the 2016 Zika virus epidemic. By prospectively enrolling case-patients, we shortened the time to enrollment, increasing the likelihood of detecting Zika virus nucleic acids to confirm Zika virus infection.

As a result, we found that an acute Zika virus infection confirmed by laboratory testing is a risk factor for developing Guillain-Barré syndrome. This is the first case-control study to find laboratory evidence showing this given the difficulty of confirming Zika virus infection among people diagnosed with GBS.

Continue reading

Can Zika Be Used To Fight Glioblastoma Brain Tumors?

MedicalResearch.com Interview with:

Milan G. Chheda, MD Assistant Professor  Department of Medicine  Oncology Division  Molecular Oncology  Department of Neurology Washington University School of Medicine in St. Louis

Dr. Chheda

Milan G. Chheda, MD
Assistant Professor
Department of Medicine
Oncology Division
Molecular Oncology
Department of Neurology
Washington University School of Medicine in St. Louis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Glioblastoma is an extremely aggressive brain tumor. Most patients die in less than two years. A longstanding challenge has been killing tumor cells that are inherently resistant to our current therapies (radiation and chemotherapy). These cells, called cancer stem cells, are extremely hardy. A longstanding dream of oncologists has been to devise a way to find them and kill them. The public health epidemic in 2015 made Zhe Zhu, post-doctoral fellow in Jeremy Rich’s lab, wonder whether Zika virus could work on cancer stem cells, that share properties with stem cells in fetal brain. Zika virus doesn’t cause significant problems in adults.

We took a lesson from nature and tested Zika virus.

Continue reading

Potential Drug-Binding Site Against Zika Virus Identified

MedicalResearch.com Interview with:

Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside.

Dr. Jikui Song

Dr. Jikui Song PhD
Assistant professor of biochemistry
University of California, Riverside.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV.

The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV.

Continue reading

Comparison Zika Outbreaks in French Polynesia, Colombia and the State of Bahia in Brazil

MedicalResearch.com Interview with:

Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China

Dr. Daihai He

Daihai He PhD
Department of Applied Mathematics
The Hong Kong Polytechnic University
Hung Hom, Kowloon
Hong Kong (SAR), China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus disease has large outbreaks in many Pacific and American countries in 2016, and the outbreaks are still on-going. Our work is conducted against this background. We compared data from three localities: French Polynesia in 2013-2014, Colombia and Brazil in 2016. We found that in French Polynesia the infection attack rate (i.e. the proportion of the population who got infected) is about 3/4, which matched previous serological studies. We then make estimation for the other two place. We found that the infection attack rate in Colombia in 2016 was most likely less than 50%. For Bahia province of Brazil, we did not arrive at a very accurate estimation, as the confidence interval is wide, and our best estimate is 30%. The relatively low infection attack rate in Colombia and Brazil implies that future outbreaks of Zika virus diseases are still possible. Thus control and surveillance efforts should be continued.

Continue reading

Human Placenta May Be Most Vulnerable To Zika In First Trimester

MedicalResearch.com Interview with:

R. Michael Roberts

Dr. R. Michael Roberts

R. Michael Roberts PhD
Curators’ Distinguished Professor
240b Bond Life Sciences Center
Columbia, Missouri 65211-7310

MedicalResearch.com: What is the background for this study?

Response: My background in placental biology and in communication between the embryo and the mother in early pregnancy made me curious about how the zika virus (ZIKV) crossed the placenta in early pregnancy to cause microcephaly. My group had been working on a laboratory model for placental trophoblast for over 10 years. We generate trophoblast from human pluripotent cells (embryonic stem cells and induced pluripotent stem cells) by exposing them to the growth factor BMP4 and two pharmaceuticals that inhibit the signaling pathways necessary to maintain pluripotency. I was curious to determine whether or not ZIKV could infect these cells, replicate, and release infectious virus, because work from my collaborator Yoel Sadovsky at the University of Pittsburgh indicated that the mature placenta was likely to be resistant to infection.

MedicalResearch.com: What are the main findings?

Response: There are, I believe two striking outcomes from this work.

One is that the results indicate that the human placenta is likely most vulnerable to infection by Zika during the first trimester. We also suggest that women whose fetus is affected from an infection occurring later in pregnancy likely had a past dengue infection. The second striking result is that the African strain of Zika may have greater virulence towards early placenta than the Asian strains, such as the ones that have spread in the New World.

The work with the virus only began when we realized that term trophoblasts lacked expression of the genes that encode the protein factors that promote flavivirus infection (ZIKV is a flavivirus, like dengue, West Nile virus), e.g. TYRO3, AXL, MERTK, and also had a poised innate immune system that would counteract virus replication. Conversely, the trophoblasts we create from embryonic stem cells had the factors that would promote virus uptake, but seemed ill-prepared to counteract virus replication once infection occurred. In other words, the early placental trophoblasts were potentially more susceptible to infection. We confirmed this hypothesis with two strains of ZIKV (an Asian strain related to the one encountered in Brazil, and an African strain often considered to be relatively benign). What was unexpected was the African strain appeared to be more virulent than the Asian strain.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Whether the early placenta could be protected by some sort of immune therapy or by prior vaccination of the mother is clearly uncertain at present. Vaccination programs have not been altogether successful when used to protect against Dengue, which is a virus related to ZIKV.

There is evidence that the early placenta is also permissive to other viruses, such as Rubella. Also there is a very interesting paper in the Journal of the American medical Association by Honein et al. that was published on December 15, 2016. In this study, the overall risk for microcephaly and other brain abnormalities in infants born to a large cohort of U.S. women exposed to ZIKV while traveling (n = 442) was 5.9 % (18), and, of these, there were no cases noted among the women known to have been infected during their second or third trimesters. In Brazil, women appear to be at risk for fetal infections by ZIKV throughout their pregnancies but this may be because they had experienced an earlier infection by Dengue. I have discussed this puzzle in the paper.

I have no disclosures to make, nor conflicts of interest regarding the research or this response to your queries.

Citation:

PNAS Plus – Biological Sciences – Applied Biological Sciences:
Megan A. Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, Alexander W. Franz, Yoel Sadovsky, Toshihiko Ezashi, and R. Michael Roberts
Vulnerability of primitive human placental trophoblast to Zika virus PNAS 2017 114 (9) E1587-E1596; published ahead of print February 13, 2017, doi:10.1073/pnas.1616097114

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Human Genetics Contributes To Zika-Induced Brain Damage

MedicalResearch.com Interview with:

Ping Wu, MD, PhD John S. Dunn Distinguished Chair in Neurological Recovery Professor, Department of Neuroscience & Cell Biology University of Texas Medical Branch Galveston, TX 77555-0620

Dr. Ping Wu

Ping Wu, MD, PhD
John S. Dunn Distinguished Chair in Neurological Recovery
Professor, Department of Neuroscience & Cell Biology
University of Texas Medical Branch
Galveston, TX 77555-0620

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika viral infection poses a major global public health threat, evidenced by recent outbreaks in America with many cases of microcephaly in newborns and other neurological impairments. A critical knowledge gap in our understanding is the role of host determinants of Zika-mediated fetal malformation. For example, not all infants born to Zika-infected women develop microcephaly, and there is a wide range of Zika-induced brain damage. To begin to fill the gap, we infected brain stem cells that were derived from three human donors, and found that only two of them exhibited severer deficits in nerve cell production along with aberrant alterations in gene expression.

Continue reading