Zika Virus Persistently and Productively Infects Primary Adult Sensory Neurons In Vitro

Abstract

Zika virus (ZIKV) has recently surged in human populations, causing an increase in congenital and Guillain-Barré syndromes. While sexual transmission and presence of ZIKV in urine, semen, vaginal secretions, and saliva have been established, the origin of persistent virus shedding into biological secretions is not clear. Using a primary adult murine neuronal culture model, we have determined that ZIKV persistently and productively infects sensory neurons of the trigeminal and dorsal root ganglia, which innervate glands and mucosa of the face and the genitourinary tract, respectively, without apparent injury. Autonomic neurons that innervate these regions are not permissive for infection. However, productive ZIKV infection of satellite glial cells that surround and support sensory and autonomic neurons in peripheral ganglia results in their destruction. Persistent infection of sensory neurons, without affecting their viability, provides a potential reservoir for viral shedding in biological secretions for extended periods of time after infection. Furthermore, viral destruction of satellite glial cells may contribute to the development of Guillain-Barré Syndrome via an alternative mechanism to the established autoimmune response.

Zika virus replicates in skeletal muscle contributing to peripheral viral amplification prior to reach neural tissue

“…Furthermore, the inability of ZIKV disturb the BBB permeability, after early life infection, reinforces the possibility of viral accesses CNS by peripheral neurons. This is also supported by the detection of ZIKV negative strain in the DRG of neonates (6 dpi), and corroborates with previous studies that demonstrated ZIKV replication in explants and neurons from DRG of ZIKV-infected mice (16, 50). In addition, it was previously demonstrated that ZIKV reaches CNS without disrupt BBB by transcytosis, interfering on its permeability only at late stages of infection (15).…”

The journey of Zika to the developing brain

“…It has been shown that ZIKV persistently infects various trigeminal and dorsal root sensory neurons. Conversely, autonomic sympathetic and parasympathetic neurons were shown to be non-permissive to infection [152]. This is supported by the finding that cells of the peripheral nervous system are much less susceptible to infection than cells of the central nervous system (CNS), with all major CNS cell types being susceptible to infection, particularly oligodendrocytes [153].…”

Zika virus has an oncolytic activity against human glioblastoma U87 cells

“…Вполне вероятно, что при использовании более высоких доз (10 7 -10 8 ТЦД 50 ) будет достигаться более эффективная репликация вируса в клетках опухоли, что в итоге может привести к лизису клеток глиобластомы и полной регрессии всех привитых ксенографтов глиобластомы. Известно, что вирус Зика способен длительно персистировать в инфицированном организме, в том числе и в клетках нервной системы (Swartwout et al, 2017) Titer, TCID 50 /mL 2 · 10 5 (8 · 10 4 -5 · 10 5 ) * 5 · 10 5 (2 · 10 5 -1.2 · 10 6 ) 2 · 10 5 (7 · 10 4 -6.5 · 10 5 ) 10 3 (6 · 10 2 -2.5 · 10 3 ) (Mazar et al, 2018). В этой работе приведены данные, свидетель ствующие о рецепторном взаимодействии вируса Зика с клеточным поверхностным гликопротеином CD24, и экспериментально доказана зависимость инфекционности вируса Зика для клеток от уровня презентации CD24 на клеточной поверхности.…”