The three parent hypothesis: Mum, Dad and Zika virus...

Ian M. Mackay & Katherine E. Arden

This week we saw a case study of a 32 year old man returning from Brazil to France who recovered from a Zika virus (ZIKV) infection.[1] Nothing to see there. 

But there was something fascinating to see when the authors pointed us to the viral loads in samples collected 2 weeks after symptom onset...

• Serum: 10^2.8 copies of viral RNA per millilitre of sample (about 631 copies/ml)
• Urine: 10^3.1 copies/ml (=1259 copies/ml)
• Semen: 10^8.6 copies/ml (=398,107,171 copies/ml)

Semen had 630,914-times more ZIKV RNA in it than serum (316,209 times more than urine) - two weeks later! And in addition to the detection of viral RNA, infectious ZIKV could be isolated using cell culture of the semen sample.

Not only was there so much more viral RNA in semen than in urine or serum, but serum remained positive 2 weeks later. That is not the norm for a ZIKV infection. Usually, viraemia (virus, or viral RNA as a surrogate for virus, in the blood) resolves within a week.[2] That suggests that in some people, ZIKV can replicate very efficiently and for a longer time than what we consider to be the average. Could this be something to do with the nature of the particular ZIKV variant of the Asian lineage circulating in Brazil? Is it just showing up because there are more cases than we've seen before. It does - yet again - flag how much we need more testing data and publications of quality from Brazil. We also really need some comparative virology studies, and more sequencing. Key puzzle pieces that are still missing.

Sexual transmission of ZIKV is rare but, as we've seen described a number of times now,[3] it is a plausible route of infection. It may also be possible that an infectious dose - currently not defined - is delivered via the semen of even low viral load mildly ill or asymptomatic men; assuming that lower viral loads correlate with few or no symptoms and assuming that there is any ZIKV in the semen of men with mild signs and symptoms, or none at all. This may lead to an infection in the partner.

What if... a ZIKV infection in the female partner leads to a foetus with congenital anomalies that begins at fertilization? What if there are in fact 3 players at conception; Mum, Dad and Zika present in the semen?

Among those studies which hopefully aim to go beyond the "scientific consensus" and use actual science to logically seek some real evidence, it would be great to see them answer:

1. What is the serostatus of the mother and father for DENV, CHIKV and ZIKV before conception?
2. Is Dad's semen positive for DENV, CHIKV or ZIKV prior to conception?
3. How do antibody levels to DENV, CHIKV and ZIKV vary during the course of the pregnancy?

It is worth considering the other two viruses, DENV and CHIKV because there has been no investigation into whether they, or cellular or antibody immune responses to them, may interact to produce the foetal anomalies seen in Brazil and French Polynesia. These three viruses have all been active at some time in these regions-sometimes at the same time.

Some things to at least consider.

References...

1. http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(16)00138-9.pdf
2. http://virologydownunder.blogspot.com.au/2016/04/usefulness-of-urine-samples-for-zika.html
3. Sexual transmission of Zika virus: implications for clinical care and public health policy
   http://www.ncbi.nlm.nih.gov/pubmed/27048746