New Zika clone could be new model for developing vaccine
Stopping the explosive spread of Zika virus - which can lead to birth defects in babies born to infected mothers - depends on genetic insights gleaned through new tools and models. Researchers at the National Institutes of Health recently cloned an epidemic strain of the virus, creating a model that can help biologists develop and test strategies for stopping the pandemic. In the latest issue of mBio, the researchers reported that the cloned virus replicated successfully in multiple cell lines, including placental and brain cells - tissue particularly vulnerable to damage from Zika. The clone will be used for the development of a live but attenuated vaccine.
"Our goal is to create long-term immunity after one short immunization," says study leader and molecular biologist Alexander Pletnev, at the National Institute of Health's National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
The goal of Pletnev's group is to create a live, attenuated vaccine similar to the ones used in humans against other harmful viruses like polio, yellow fever, and Japanese encephalitis. Following up on their lab studies, Pletnev and his collaborators recently began mouse studies of the cloned virus. Pletnev says he invites other researchers to use his lab's ZIKV clone to investigate and ultimately stop the harm caused by Zika.
The virus was first identified nearly 70 years ago in Uganda, but for decades it circulated only in a small geographic area in equatorial Africa and Asia, and mostly among primates. The current epidemic began in early 2015 in Brazil, and since then has spread throughout South and Central America. In February 2016, the World Health Organization declared the pandemic a public health emergency. Five months later, the US Centers for Disease Control and Prevention reported the first case of mosquito-borne infection in the US in residents of Florida, in a neighborhood near Miami. (The virus can also be transmitted through sex.)
The biological behavior of viruses is often unpredictable, which makes it difficult for scientists to figure out how to stop them, says Pletnev. Zika belongs to the Flavivirus group of viruses, which also includes West Nile, dengue, and yellow fever. Viruses in this family each have a single strand of RNA, but they're notoriously difficult to manipulate and clone. With the tools of reverse genetics, biologists can study single-stranded RNA by using viral complementary DNA, or cDNA. Flaviviruses, however, are often toxic to their bacterial hosts, and biologists have pursued a variety of ways around the problem.
Pletnev and his group, including researchers from the University of Texas and the US Food and Drug Administration, began with a viral strain collected from an infected, febrile patient in Brazil in 2015. To reduce toxicity and increase the stability of the ZIKV cDNA clone during growth in Escherichia coli bacteria, they added introns - or specific nucleotide sequences - to the full viral cDNA genome. High-throughput sequencing revealed that the virus derived from the cDNA clone had less genetic diversity than its wild-type parent strain, and subsequent experiments showed that the clone was attenuated, compared to its parent.
The researchers made a few more genetic tweaks to customize their clone to grow in Vero cells - a line derived the kidneys of African green monkeys, commonly used in human vaccine manufacture.
In addition to their work on Zika, which began in early 2016, Pletnev's group has worked extensively on other Flaviviruses. They produced a vaccine for West Nile virus, currently in clinical trials, and have worked on developing vaccines against St. Louis and Japanese encephalitis. Their current work on Zika was funded by the Division of Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Source: American Society for Microbiology
Articles on the same topic
- FSU research team makes Zika drug breakthrough8 years ago
- NIH collaboration helps advance potential Zika treatments8 years ago
- New hope for Zika treatment found in large-scale screen of existing drugs8 years ago
- Researchers report new Zika complication8 years ago
- New mouse model of Zika sexual transmission shows spread to fetal brain8 years ago
- Zika virus may persist in the vagina days after infection8 years ago
- Zika virus detected in newborn until 2 months after birth8 years ago
- Yale team discovers how Zika virus causes fetal brain damage8 years ago
- In some genetic cases of microcephaly, stem cells fail to launch8 years ago
- Study suggests that brain damages caused by Zika virus congenital infection go beyond microcephaly8 years ago
- New report details pre- and postnatal brain defects from Zika virus8 years ago
Other sources
- Mosquitoes Can Pass Zika Along To Offspringfrom PopSci8 years ago
- WHO's Zika emergency panel convenes on Thursdayfrom CBC: Health8 years ago
- Singapore Says It Expects More Zika Casesfrom NY Times Health8 years ago
- Zika virus: Singapore confirms 41 locally transmitted casesfrom BBC News: Science & Nature8 years ago
- Zika Can Be Transmitted by Female Mosquito to Her Eggs, Study Saysfrom NY Times Science8 years ago
- Mosquitoes Can Infect Their Eggs With Zikafrom MSNBC: Science8 years ago
- 3 Drugs identified to potentially fight Zika virusfrom UPI8 years ago
- New hope for Zika treatment found in large-scale screen of existing drugsfrom Science Daily8 years ago
- Two Existing Drugs Might Stop Zika Infectionsfrom MSNBC: Science8 years ago
- Zika outbreak: Singapore steps up prevention as cases rise to 56from CBC: Health8 years ago
- Locally transmitted Zika virus infects 41 in Singaporefrom CBC: Health8 years ago
- Locally transmitted Zika virus infects 41 in Singaporefrom AP Health8 years ago
- All blood in the U.S. should be screened for Zika, FDA saysfrom LA Times - Science8 years ago
- Acute virus infection associated with sensory polyneuropathy, Zika experts sayfrom Science Daily8 years ago
- Sex partner with no Zika symptoms transmits virus: CDCfrom UPI8 years ago
- FDA recommends all blood donations be tested for Zikafrom UPI8 years ago
- All Donated Blood in U.S. Will Be Tested for Zikafrom NY Times Science8 years ago
- All Donated U.S. Blood Should Be Tested For Zika, FDA Advisesfrom PopSci8 years ago
- Zika virus may persist in the vagina days after infectionfrom Science Blog8 years ago
- FDA expands Zika screening to all US blood centersfrom AP Health8 years ago
- Zika outbreak: FDA advises screening for all blood centresfrom CBC: Health8 years ago
- Zika outbreak: Miami teams increase mosquito control efforts at stadiumsfrom CBC: Health8 years ago
- Animal research yields clues to sexual spread of Zikafrom UPI8 years ago
- Zika virus detected in newborn until 2 months after birthfrom Science Daily8 years ago
- Yale team discovers how Zika virus causes fetal brain damagefrom Biology News Net8 years ago
- In some genetic cases of microcephaly, stem cells fail to launchfrom Biology News Net8 years ago
- In Babies, Zika Can Linger for Months, Brazilian Case Suggestsfrom Live Science8 years ago
- In some genetic cases of microcephaly, stem cells fail to launchfrom Science Daily8 years ago
- Ultrasounds Show What Zika Is Doing To Brains In The Wombfrom PopSci8 years ago
- In Some Genetic Cases of Microcephaly, Stem Cells Fail to Launchfrom Science Blog8 years ago
- In Florida Keys, Some Worry About ‘Science and Government’ More Than Zikafrom NY Times Health8 years ago
- New Zika clone could be new model for developing vaccinefrom Science Daily8 years ago
- Brain damages caused by Zika virus congenital infection go beyond microcephalyfrom Science Daily8 years ago
- New report details pre- and postnatal brain defects from Zika virusfrom Science Daily8 years ago
- Scans show range of Zika-linked infant brain defectsfrom UPI8 years ago
- Zika, a Formidable Enemy, Attacks and Destroys Parts of Babies’ Brainsfrom NY Times Science8 years ago