|HSV-2 virus particle. (Courtesy of Linda M. Stannard, University of Cape Town) via Virology Online|
New research has discovered an important risk factor for Zika virus crossing the placental barrier: co-infection with Herpes simplex virus-2 (HSV-2). In the study, the researchers used a first trimester trophoblast cell line that has been well characterized and infected it with two different strains of Zika virus and one of Yellow fever virus. The cells infected with Yellow fever virus survived despite the virus actively replicating whereas both strains of Zika induced apoptosis in infected cells. The researchers also discovered that infection with Zika inhibited the type I-β interferon pathway (a signaling protein that triggers an immune response against viral infection). Zika infection also interfered with trophoblast differentiation into spheroids (something that this cell line does under the right conditions).
These are very important findings that help us understand the biology of Zika. It's when researchers tested Zika virus infection in cells already infected with HSV-2 that they found something very interesting. When the cells were infected with HSV-2, the expression of three receptors, required for flavivirus entry into cells, were increased. To test to see if this helps Zika virus cross the placental barrier, mice were infected with Zika virus in either a single infection or after prior HSV-2 infection. Zika viral RNA levels were low in the mice only infected with Zika; however, in the mice previously infected with HSV-2, the Zika virus RNA titer was incredibly high. These results suggest that prior HSV-2 infection could aid Zika virus in crossing the placental barrier.
The researchers tested HSV-2 infection because HSV-2 is prevalent in NE Brazil where microcephaly cases seem to be higher than in other places. The researchers hypothesize that the prevalence of HSV-2 in NE Brazil could help account for the increase in Zika-associated microcephaly cases there. Prior HSV-2 infection could be a risk factor that may make Zika infection worse in pregnant mothers, so these are very important findings. Hopefully researchers will investigate further with retrospective studies to see if there is an association here.