June 25, 2024

Whole Family

Trailblazing Family Excellence

USF Health researchers show how the placenta protects fetus in the womb against viral infections

3 min read

Give credit to your dad’s gene for keeping you safe during those long months in your
mother’s womb.

Because without this genetic warrior, you might have succumbed to any number of viral
infections that otherwise could be fatal to a fetus. A new paper published this week
in the journal Cell Host & Microbe explains the mechanisms behind this anti-viral protection.

“What’s unique about this gene is how it produces a form of defense for the baby in
the womb,’’ said Hana Totary-Jain, PhD., associate professor of Molecular Pharmacology
and Physiology and Heart Institute at the USF Health Morsani College of Medicine and
senior author of the paper.

Their research focused on viruses that affect a pregnant mother and consequently her
fetus, which are highly vulnerable to infection because their immune systems are immature.
Some viruses, including Zika, rubella, and other serious infections, are rarely transmitted
from mother to fetus in utero and can cause devastating consequences.

But the biological processes that protect a fetus from most viral infections are less
clear. In the new paper, titled “SINE RNA of the imprinted miRNA clusters mediates
constitutive type III interferon expression and antiviral protection in hemochorial
placentas,’’ Dr. Totary-Jain and her team describe how a certain gene in the placenta
is always armed for the battle.

“The placenta, in human and in mouse, is the first organ the fetus develops, and it
is constantly exposed to maternal blood. This increases the chances of transmitting
viral infections from the mother to the fetus. Therefore, the placenta has evolved
robust defense mechanisms to prevent this transmission. We discovered a gene in the
placenta that is expressed only from the paternal allele and produces a viral mimicry
response. It tricks the placenta into thinking it’s infected and induces a constant
state of antiviral defense”, Dr. Totary-Jain explained.

“So when we turned on this gene in other cells, we could protect the cells from several
viruses. This is evolution’s way of protecting the baby. Without it, chances are you
wouldn’t have made it into childbirth.’’

Ishani Wickramage, a PhD candidate in Dr. Totary-Jain’s laboratory and a lead author
of the study added: “This research fills the gap in our knowledge about how many viruses
that may infect a pregnant mother, including SARS-CoV-2, only rarely affect the fetus.’’

“Learning more about how the placenta shields the fetus from viruses also has important
implications beyond childbirth,” said Dr. Charles Lockwood, MD, MHCM, one of the paper’s
authors, who also is dean of the Morsani College of Medicine and executive vice president
of USF Health.

“This is a novel placental mechanism that protects the developing fetus from transplacental
transmission of most viruses,” Dr. Lockwood said. “This is the kind of knowledge that
could lead to the development of new anti-viral medications to fight viruses that
can be deadly for fetuses and newborn babies.”

This work was supported by a grant from the National Institutes of Health. Dr. Totary-Jain
and a team of researchers at USF spent five years investigating this intriguing phenomenon
in collaboration with Dr. Thomas Tuschl’s lab at Rockefeller University, who performed
the sRNAseq and bioinformatic analysis, including researcher Klaas Max and Kemel Akat;
and Drs. Kimiko Inoue and Atsuo Ogura from RIKEN and University of Tsukuba, Japan,
who provided the mouse model that was used to show that the mouse placenta also developed
the same mechanism to protect the fetus from viral infections.

Other USF Health members of the research team are: Jeffrey VanWye; John H. Lockhart;
Ismet Hortu; Ezinne F. Mong; John Canfield; Hiran M. Lamabadu Warnakulasuriya Patabendige;
Ozlem Guzeloglu-Kayisli; and Umit A. Kayisli.

— Story by Kurt Loft for USF Health News

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