The mitotic spindle: linking teratogenic effects of Zika virus with human genetics?
BACKGROUND
Recently, an association between Zika virus infection and microcephaly/ocular findings was found to be reasonable e.g. because of the demonstration that the virus was found in the brain of a fetus after presumed maternal infection. Although there is no proof yet for a causal relationship, for an appropriate risk calculation efforts are urgently needed to either establish or disprove this assumption.


OBJECTIVE
On the basis of inherited syndromes combining microcephaly with ocular findings similar to those associated with Zika infections, we have hypothesized that the impairment of the proper function of the mitotic apparatus is a possible mechanism by which Zika can exert teratogenic effects.


METHODS
A bundle of well-known cytogenetic and molecular-cytogenetic methods (e.g. formation of micronuclei, chromosomal lagging, immunofluorescence of centrosomes) to evaluate proper function, maintenance, and establishment of the mitotic spindle poles can be applied on infected cells. Also, the viral proteins can be tested for their possible interaction with proteins encoded by genes involved in inherited syndromes with microcephaly and ocular findings resembling those in presumed cases of intrauterine ZIKV infection.


CONCLUSIONS
Once proved, this hypothesis allows for a targeted approach into mechanisms of possible relevance as e.g. if different strains of the virus are implicated in the teratogenic effects to the same or a different extent.
Centre for Human Genetics, University of Bremen, Leobener Str. ZHG, D-28359 Bremen, Germany ; Institute of Medical Genetics, University Rostock Medical Center, Ernst-Heydemann-Strasse 8, D-18057 Rostock, Germany.
Joern
J
Bullerdiek
Laboratory of Virus Research, University of Bremen, Leobener Straße/UFT, 28359, D-28359 Bremen, Germany.
Andreas
A
Dotzauer
Institute of Medical Genetics, University Rostock Medical Center, Ernst-Heydemann-Strasse 8, D-18057 Rostock, Germany.
Ingrid
I
Bauer
Chorioretinopathy; Genetics; Mechanisms; Microcephaly; Phenocopy; Syndromes; Zika virus