Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells

Abstract

The recent Zika virus (ZIKV) epidemic has highlighted the poor knowledge on its physiopathology. Recent studies showed that ZIKV of the Asian lineage, responsible for this international outbreak, causes neuropathology in vitro and in vivo. However, two African lineages exist and the virus is currently found circulating in Africa. The original African strain was also suggested to be neurovirulent but its laboratory usage has been criticized due to its multiple passages. In this study, we compared the French Polynesian (Asian) ZIKV strain to an African strain isolated in Central African Republic and show a difference in infectivity and cellular response between both strains in human neural stem cells and astrocytes. Consistently, this African strain led to a higher infection rate and viral production, as well as stronger cell death and anti-viral response. Our results highlight the need to better characterize the physiopathology and predict neurological impairment associated with African ZIKV.

Replication of early and recent Zika virus isolates throughout mouse brain development

“…Induction of caspase 3 cleavage occurred mostly within the cells that surround the virus-infected cell (Fig. 3), which has also been suggested by the results of other studies (30,31). These regions of apoptosis were confined to areas marked by ZIKV-E staining, as seen in the neocortex of an organotypic slice infected with the Malaysian isolate (Fig.…”

Vulnerability of primitive human placental trophoblast to Zika virus

“…The likely involvement of ZIKV in neurological disease is consistent with its ability to infect and replicate within human cortical neuronal progenitor cells and slow their growth (9,10), infect human neurospheres and brain organoids (9,(11)(12)(13), and colonize the developing brain of mouse fetuses injected directly with the virus (14). Importantly, an African lineage strain (MR766) of ZIKV from Uganda (ZIKV U ) is as at least as capable of infecting human neural progenitor cells in vitro as strains of Asian origin (10,12,13,15), even though there is no indication that the former causes brain developmental abnormalities in infants.…”

“…We have no ready explanation for this observation, although it is clearly of interest, as it is the Asian strains of ZIKV that have been linked to fetal and pediatric brain abnormalities. Others have noted similar differences in virulence between an African and Asian strain on human neural cells and astrocytes and suggested that African strains should not necessarily be dismissed as benign with regard to causing neurological impairment (15).…”

Using brain organoids to understand Zika virus-induced microcephaly

“…A number of studies have since modeled ZIKV infection using human NPC monolayer and neurosphere cultures, acute fetal brain slices, and brain organoids (Barrows et al, 2016;Cugola et al, 2016;Dang et al, 2016;Garcez et al, 2016;Hanners et al, 2016;Liang et al, 2016;Onorati et al, 2016;Qian et al, 2016;Retallack et al, 2016;Simonin et al, 2016;Wells et al, 2016) (Fig. 1).…”

“…Moreover, owing to the long-term nature of organoid culturing, small perturbations in culture conditions could potentially change the outcome significantly. While efforts have been made to generate brain region-specific organoids under defined conditions, it is important to establish common standards of organoid quality by carefully characterizing multiple aspects, including lineage Barrows et al, 2016;Garcez et al, 2016;Hanners et al, 2016;Onorati et al, 2016;Simonin et al, 2016;Tang et al, 2016;Wells et al, 2016;Xu et al, 2016;Zhang et al, 2016 Fig. 1.…”