Zika Virus Infection Preferentially Counterbalances Human Peripheral Monocyte and/or NK Cell Activity

Abstract

ZIKV reemerged in recent years, causing outbreaks in many parts of the world. Alarmingly, ZIKV infection has been associated with neurological complications such as Guillain-Barré syndrome (GBS) in adults and congenital fetal growth-associated anomalies in newborns. Host peripheral immune cells are one of the first to interact with the virus upon successful transmission from an infected female Aedes mosquito. However, little is known about the role of these immune cells during infection. In this work, the immune responses of monocytes, known target cells of ZIKV infection, were investigated by high-density transcriptomics. The analysis saw a robust immune response being elicited. Importantly, it also divulged that monocytes prime NK cell activities during virus infection. Removal of monocytes during the infection changed the immune milieu, which in turn reduced NK cell stimulation. This study provides valuable insights into the pathobiology of the virus and allows for the possibility of designing novel targeted therapeutics.

Immunological observations and transcriptomic analysis of trimester‐specific full‐term placentas from three Zika virus‐infected women

“…Interestingly, EGF and IP‐10 are typically expressed at higher levels in women carrying a foetus with developmental anomalies . The association of neutrophils with the acute phase should also be given more attention since most studies have focused on the role of monocytes during ZIKV infection thus far . Neutrophils have been shown to infiltrate the central nervous system of ZIKV‐infected immunocompromised mice and may therefore be a causative element in Zika‐induced neurologic damage.…”

Longitudinal Study of Cellular and Systemic Cytokine Signatures to Define the Dynamics of a Balanced Immune Environment During Disease Manifestation in Zika Virus–Infected Patients

“…The role of blood immune cells in ZIKV infection is understudied, but monocytes are a reported cellular target for ZIKV [ 11–14 , 19 ]. Moreover, monocytes have been shown ex vivo to modulate the host immune response during ZIKV infection [ 13 ]. High levels of MCP-1 and GM-CSF detected in patients during the acute phase further confirm the role of monocytes during infection.…”

Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures

“…Further definition of molecular signatures characteristic of flaviviral immunity and susceptibility phenotypes is essential to guide development of improved diagnostics, therapeutic interventions and vaccines for Zika. Investigations to understand the ferocity of the Zika epidemic may include ongoing research areas of epidemiological factors such as co-circulating pathogens [94], cellular signaling pathways antagonizing the Type I or Type II IFN responses [80,95,96], or other immune pathways such as RIG-I [97], viperin [98], or pathogenic cellular interactions including CD8 cells in pathology in neurons [99] or monocytes driving NK cells anti-Zika responses [100].…”