Viral Hijacking of Formins in Neurodevelopmental Pathologies

Auditory findings associated with Zika virus infection: an integrative review

“…The search strategy initially identified 157 records, which, at the end of the selection process, resulted in the inclusion of 27 articles 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ( Fig. 1 and Appendix 1 ).…”

“…1 and Appendix 1 ). Three of these studies concerned acquired ZIKV infection in adults ( n = 6), 5 , 6 , 7 16 studies concerned prenatal exposure to ZIKV infection ( n = 962) 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 41 , 42 , 43 , 44 , 45 , 50 , 51 nine studies included considerations on the pathogenesis of auditory impairment 6 , 7 , 8 , 9 , 42 , 43 , 46 , 47 , 52 and 17 studies included recommendations on hearing screening and follow up for patients with congenital or acquired ZIKV infection 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 , 16 , 42 , 44 , 46 , 48 , 49 , 52 , 53 , 55 ( Table 1 ). Most of the nineteen studies on acquired or prenatal exposure to ZIKV were considered of low or moderate quality, both in general and in relation to the performed auditory evaluations and the quality of scientific evidence for the prevalence of hearing impairment in children prenatally exposed to ZIKV is insufficient ( Table 1 , Table 2 ).…”

“… “In summary, ZIKV exposure is associated with HL in infants and adults. Hearing loss can occur as a result of the damage to the inner ear or auditory nerve, by a direct viral effect or mediated by an autoimmune process as demonstrated in the case of other viral infections.” Racicot et al (2017); USA 47 “Mutations affecting Diaph expression (Diaph 1 and 3) can cause microcephaly and hearing loss in humans and mice.” “Neurotropic viruses can significantly affect NPC (neuroprogenitor cell) functions, including cell fate decisions, proliferation, migration and survival.” “Most viruses express gene products that can functionally ‘hijack’ the Rho-Diaph system, sequestering these proteins for the purpose of modifying the actin cytoskeleton to promote viral entry, assembly and spread.” “We hypothesize that viral ‘repurposing’ of Diaphs disrupts normal host cellular functions, resulting in premature NPC differentiation or apoptosis, as mentioned previously. If viruses sequester Diaphs in NPCs, preventing them from executing their normal cellular functions, it follows that neurological phenotypes associated with these infections would be similar to those caused by genetic mutations of Diaphs.” Leal et al (2019); Brazil 52 “In all studies, it seems clear that the auditory impairment is closely related to the presence of microcephaly and its severity.” “An issue not yet clarified is the topography of the lesion responsible for hearing loss produced by ZikV infection.…”

“…The hypothesis raised by Racicot et al, 47 suggesting that the ZIKV causes sequestration and redirection of proteins (Diaphanous-related formins – Diaphs) in progenitor neural cells, determining microcephaly or hearing loss in humans, similar to what is noted in individuals presenting mutations in the genes responsible for the expression of these proteins, opens a promising field to be explored in future research.…”

A Review of Hearing Loss Associated with Zika, Ebola, and Lassa Fever

“…21 The most well-supported hypothesis of the mechanism for Zika-related HL is direct viral invasion of neurons in the auditory pathway. [77][78][79] The virus has been shown to have preference for undifferentiated neurons, which may explain the devastating complications resulting from congenital cases in comparison with adults and may serve as a possible explanation for the observed auditory neuropathy findings. 28,80 In contrast to the auditory neuropathy observed in Zika, HL associated with Ebola and LF is similar to common viral-mediated etiologies of HL and can be easily detected with traditional hearing screening.…”