Detection of a novel African-lineage-like Zika virus naturally infecting free-living neotropical primates in Southern Brazil

Abstract

Mosquito borne flaviviruses cause a series of important diseases in humans and animals. These viruses are maintained in cycles involving replication in mosquito and in vertebrate hosts. Most natural hosts are vertebrate animals living in sylvatic or peridomestic environments. Human contact with these environments may result in host shifts that lead to the establishment of urban transmission cycles. Zika virus is a Flavivirus that persists in nature in a transmission cycle involving non-human primates (NHP). Its recent emergence in Brazil has shed light upon the importance of surveying this agent in Brazilian sylvatic environments. Here we present histopathological and molecular evidence that free ranging howler monkeys (Alouatta guariba) in Southern Brazil are infected by ZIKV closely related to African lineage MR766. Nine NHP were nested RT-PCR positive for ZIKV RNA. Sequence analysis revealed 96 to 98% identity to ZIKV MR766 and 85% identity to ZIKV P6-740, the current epidemic strain. The affected howler monkeys presented discrete inflammatory infiltrates in several tissues and immunohistochemichal (IHC) labeling of viral antigen was observed in placenta. These findings point to the circulation of African lineage Zika virus in the Americas in non-human primates. And raises the possibility that ZIKV was introduced into the Americas on more than one occasion. 1

African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques

“…African-lineage ZIKV should be considered a threat to pregnant individuals and their infants, which should be taken into account when one is providing public health guidance. While African-lineage ZIKV had been thought to be geographically confined to Africa, recent studies have identified sequences of African-lineage ZIKV in South America ( 18 , 19 ). This highlights the need for continuing study of ZIKV of both genetic lineages.…”

“…In the July 2019 epidemiological update on ZIKV, the WHO identified the assessment of fetal outcomes following infection with African-lineage viruses as a priority ( 17 ). This is underscored by the recent discovery of African-lineage ZIKV sequences in South America, including evidence of fetal harm in a nonhuman primate naturally exposed to an African strain of ZIKV most closely related to the type strain, MR766 ( 18 , 19 ). While the ability of African-lineage ZIKV to infect the maternal-fetal interface and cause fetal harm has been rigorously studied in cell culture and immunocompromised mice, it remains unclear how translatable these findings are to humans.…”

Infection of the maternal-fetal interface and vertical transmission following low-dose inoculation of pregnant rhesus macaques (Macaca mulatta) with an African-lineage Zika virus

“…Of the two distinct genetic lineages of ZIKV, only Asian-lineage ZIKV is currently associated with congenital infection in humans [13]. Recently, African-lineage ZIKV has been detected in Brazil [14][15] [16]. The novel detection of African-lineage ZIKV outside the African continent demonstrates the potential of a new outbreak and underscores the need to further evaluate the threat that African-lineage ZIKV poses to pregnant people.…”

African-lineage Zika virus replication dynamics and maternal-fetal interface infection in pregnant rhesus macaques

“…This data suggests that African-lineage ZIKV poses a threat to women and their infants, which should be taken into account when providing public health guidance. While African-lineage ZIKV had been thought to be geographically confined to Africa, recent studies have identified Africanlineage isolates in South America (16,17). This highlights the need for continuing study of ZIKV of both genetic lineages.…”

“…In the July 2019 epidemiological update on ZIKV, the WHO identified the assessment of fetal outcomes following infection with African-lineage viruses as a priority (15). This is underscored by recent findings of African-lineage isolates in South America, including evidence of fetal harm in a non-human primate naturally exposed to an African strain of ZIKV most closely related to the prototype strain, MR766 (16,17). While the ability of African-lineage ZIKV to infect the 108 maternal-fetal interface and cause fetal harm has been rigorously studied in cell culture and immunocompromised mice, it remains unclear how translational these findings are to humans.…”