In one of the first detailed analyses of a CZS case, investigators demonstrate the presence of Zika viral RNA in the spleen, lungs, liver and muscle.
A study published in Clinical Infectious Disease demonstrated that epithelial cells are susceptible to congenitally acquired Zika virus, and researchers demonstrate that the virus was isolated from a pool of tissue samples from the heart, lungs and kidneys, suggesting that one of them may represent an important niche for Zika virus replication in immunosuppressed adults.
This single-participant study focused on a deceased 30-week-old newborn. Various fresh tissue samples were acquired (2 hours post-mortem) and paraffin-embedded for in situ microscopy experimentation. At a 30-week gestation period, the head circumference was 23.5 cm, and micrognathia, retrognathia, low-set ears, a depressed nasal bridge, and arthrogryposis were evident. A structural survey of the brain showed a smooth cortical surface, hypoplastic central lobes, and brain stem and bilateral ventricular enlargement.
Microscopy results showed extensive granular calcification in the cortical and subcortical white matter, accompanied by positive Iba1 immunostaining for active microglia. Infrequent inflammation of capillaries in the perivascular space was observed, along with positive staining for F4-80 (eluding to monocyte movement from capillary lumen to perivascular space). TUNEL staining showed many apoptotic cells. RNA studies detected Zika virus in the cerebral cortex, thymus, lungs, kidneys, adrenal glands, and spleen, while the small intestine and liver were negative. Epstein-Barr virus presence was positive in the cerebral cortex and liver samples, and human herpesvirus 6 was present in the thymus, kidneys, adrenal glands, and liver samples. The Zika virus genome was identified in the brain tissue. Immunostaining for the viral envelope protein E was positive in the cortex (specifically around calcified areas and in macrophages localized in perivascular infiltrates), kidneys (both medullar and cortical tubules), and lungs (cytoplasm of bronchial epithelial cells). Of note, neurons, ependymal cells, and thymus cells stained mildly positive. Neurons and ependymal cells stained positive for TUNEL. Reverse transcriptase-qPCR immune-testing confirmed the presence of ZIKV in brain and kidney tissue.
Comprehensively, these results suggest that (in congenitally infected fetuses) Zika virus can replicate in human kidneys and metastasize to other fetal organs.
This study included data based on a single fetus, therefore more research is necessary to understand the association between Zika virus replication in fetal kidneys, renal damage, and other pathological changes.
Valdespino-Vázquez MY, Sevilla-Reyes EE, Lira R, et al. Congenital Zika Syndrome and Extra-CNS detection of Zika virus in a pre-term newborn in Mexico [Published online September 4, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy616/5090674