Fetal Harm In Zika Virus Infection During Pregnancy Related To Maternal Immunosuppression

Highlights:

• During pregnancy, a woman’s immunity is naturally suppressed so that her body does not mount an immune response and reject the fetus, which may be perceived as a foreign entity.
• Zika virus infection further lowers already weak immunity, thus enabling the virus to spread and cause serious harm to the fetus.//

Zika virus infection in pregnancy is particularly serious since the organism severely suppresses the mother’s already weak immune system (almost similar to HIV), helping the virus to multiply and spread, thereby increasing the risk of harm to the fetus with resultant birth defects. The current study was conducted by the Keck School of Medicine of USC under Dr Jae Jung, Distinguished Professor and chair of the Department of Molecular Microbiology and Immunology at the Keck School of Medicine and the findings appear in Nature Microbiology in August 2017.

Earlier Clinical Trials Have Not Included Pregnant Women – Correcting This Lapse

One of the main reasons that lots of funds and effort is being invested in Zika virus research and vaccine development is because of the severe harm it causes to the fetus during pregnancy. However, none of the Phase I clinical trials have included pregnant women, which is rather surprising according to senior author Dr Jung.

"The Zika virus vaccines in development seem to be highly effective, but they are being tested among non-pregnant women with different body chemistry compared to pregnant women," Jung said. "It’s feasible the recommended vaccine dose -- though effective for non-pregnant women -- may not be potent enough for pregnant women because their bodies are more tolerant of viruses."

Testing The Zika Virus In Blood Samples Of Pregnant Women

The research team tested the effects of African and Asian Zika virus strains in blood samples of healthy men, non-pregnant women and pregnant women between 18-39 years. The blood samples were analyzed when the infection was at the peak.

• The study included the blood of 30 pregnant patients (10 from each trimester) diagnosed with the Asian Zika virus infection.

• The virus was seen to target the CD14 surface marker positive blood monocytes (a type of white blood cell) which transform to macrophages in the tissues of the body under appropriate conditions. These cells are essentially scavenging cells that swallow viruses, bacteria and cellular debris and ensure that the infection is overcome and body remains healthy.

• The virus promotes the conversion of these white cells to M2 macrophages which indicate to the immune system that the threat is over and turns down the immunity allowing the immune system to relax.

• This false M2 signal to the immune system enables the Zika virus to rapidly replicate and spread and cause serious maternal and fetal harm; the levels of immunity suppressing M2 macrophages is already high in a pregnant woman (to prevent rejection of the fetus) and Zika virus infection further incapacitates the already weak immunity.

• The Asian Zika virus strain was found to be much more malicious than the African strain. The African Zika virus strain suppressed the immunity by about 10 percent. On the contrary, for expectant mothers infected by the Asian Zika virus, nearly 70 percent of the immune system was suppressed.

• The Asian strain’s immunosuppressive effect was significantly higher in the first and second trimester of pregnancy in comparison to non-pregnant women. However in the third trimester, the effect on the blood of pregnant versus non-pregnant women remained the same.

Earlier studies by others have shown that Zika virus infection during the first and second trimesters of pregnancy is associated with increased incidence of fetal abnormalities.

• The blood samples of infected pregnant women showed markedly higher expression of the ADAMTS9 and FN1 genes, known to be associated with pregnancy complications, namely underweight newborns and prolonged or complicated baby delivery by hyper expression of ADAMTS9 gene and uterine abnormalities leading to unusually small babies and pre-eclampsia (high maternal blood pressure) by increased FN1 gene expression.

Scope Of The Study

• The findings of the study establish the known fact that Zika virus infection in Pregnancy, especially in the first and second trimesters is serious both for the mother and the baby.

• The study highlights the importance of controlling mosquito borne diseases which are on the rise and can cause severe maternal and fetal mortality and morbidity.

Though fetal microcephaly (small fetal head) has been reported widely leading to brain damage, other equally grave birth defects have been reported such as formation of calcium clumps in the brain of newborns that results in brain damage and developmental delays, underscoring the need for urgent preventive and control measures to limit spread of Zika virus infection.

In conclusion, Dr Suan-Sin Foo, lead author of the study and a research associate in the Jae Jung Lab opines that the findings of the current study should be an eye opener to initiate appropriate measures to protect the health of the pregnant woman and the fetus from this deadly disease.

Source-Medindia