Baker Institute for Animal Health


Schang lab publishes recent finding on Zika virus in Journal of Virology

Dr. Consuelo Correa-Sierra(left), research associate and Dr. Malgorzata "Gosia" Rychlowska(right), research associate who conducted the work for this project, appear in the Schang lab at the Baker Institute for Animal Health. Photo by Rachel Philipson

The Zika virus (ZIKV), a mosquito-born RNA virus, was first identified in 1947. The first documented human infection was discovered in 1954, and was associated with mostly mild and asymptomatic infections. That is, however, until the more recent international epidemic in 2015-2018, revealed evidence of associating ZIKV infection with the congenital neurodevelopmental pathologies currently referred to as a congenital ZIKV syndrome (CZS), most significantly resulting in microcephaly. 

Zika virus is a mosquito-born RNA virus.
Photo by Егор Камелев at unsplash.

Although the most obvious negative consequence of Zika virus is microcephaly in babies born to mothers first infected during pregnancy, other neurological defects are frequently present, all of which result in serious life-long health and welfare consequences.

Microcephaly results from the loss of neuronal progenitor cells at the time when the fetal brain is developing, which lead to fewer neurons in the newborn and adult brain. Most cases of microcephaly are sporadic and have unknown causes, but genetic defects are the most frequently identified cause of microcephaly. A subset of these genetic defects is in a DNA repair enzyme, PNKP.  This is not surprising, as DNA damage itself results in neuronal pathologies and mutations in PNKP affect the ability to repair DNA damage.

Dr. Malgorzata "Gosia" Rychlowska
research associate conducting
research on Zika. 

In this work, Dr. Malgorzata "Gosia" Rychlowska, research associate, Dr. Luis Schang, along with the team of Schang lab members at the Baker Institute for Animal Health, shows that Zika virus infection of the neuronal progenitor cells induces DNA damage and functional depletion of nuclear PNKP, which prevents the repair of the damage. Moreover, it also stimulates the neuronal progenitor cells to divide even in the presence of the unrepaired DNA damage. The net result is that the neuronal progenitors that attempt to divide end up suffering of mitotic catastrophe, an eventually lethal failed attempt to divide. Thus, this paper presents a unifying model for the mechanisms of microcephaly induced by Zika virus, PNKP mutations, or DNA damage, suggesting the possibility of a common approach to manage them all by focusing on the common final event, unrepaired DNA damage.

Luis M. Schang, MV, Ph.D. Professor of Chemical Virology
at the Baker Institute for Animal Health

Read the full paper, Zika Virus Induces Mitotic Catastrophe in Human Neural Progenitors by Triggering Unscheduled Mitotic Entry in the Presence of DNA Damage While Functionally Depleting Nuclear PNKP,  in the Journal of Virology here.