Evidence for henipavirus spillover into human populations in Africa

Abstract

Zoonotic transmission of lethal Henipaviruses (HNV) from their natural fruit bat reservoirs to humans has only been reported in Australia and South/Southeast Asia. However, a recent study discovered numerous HNV clades in African bat samples. To determine the potential for HNV spillover events among humans in Africa, here we examine well-curated sets of bat (Eidolon helvum, n=44) and human (n=497) serum samples from Cameroon for Nipah virus (NiV) cross-neutralizing antibodies (NiV-X-Nabs). Using a VSV-based pseudoparticle seroneutralization assay, we detect NiV-X-Nabs in 48% and 3-4% of the bat and human samples, respectively. Seropositive human samples are found almost exclusively in individuals that reported butchering bats for bushmeat. Seropositive human sera also neutralize Hendra virus and Gh-M74a (an African HNV) pseudoparticles, as well as live NiV. Butchering bat meat and living in areas undergoing deforestation are the most significant risk factors associated with seropositivity. Evidence for HNV spillover events warrants increased surveillance efforts.

Molecular recognition of human ephrinB2 cell surface receptor by an emergent African henipavirus

“…Although sequence information revealed the presence of novel paramyxoviruses from all major mammalian Paramyxovirinae genera, the putative identification of at least 19 novel and divergent clades of HNLVs in Africa is arguably the most surprising (2). These studies have led to a reassessment of the risk that emerging HNVs or HNLVs pose to human populations (2,12). The early symptomology of HNV infections-fever and headache-cannot be easily differentiated from the symptomatic noise inherent in the pathogen-rich areas of tropical Africa.…”

“…Notably, none of our polyclonal or monoclonal antibodies made against NiV cross-reacted with GhV-G (Fig. 1) or cross-neutralized GhVpp infection (12). Similarly, anti-NiV/-HeV polyclonal and monoclonal neutralizing antibodies also did not neutralize CedV, another HNLV also distantly related to NiV/HeV (≤30% sequence identity in the G protein) (3).…”

“…The remarkably high seroprevalence (∼40%) of HNV cross-reactive antibodies and the localization of many E. helvum communities near African towns and cities underscores the potential risk of spillover events into human populations (11,12). Indeed, NiV cross-neutralizing antibodies have been detected in the sera of humans living in Cameroon (12). That these antibodies were found exclusively in individuals at high risk for zoonotic transmission, such as those that slaughter bats for bushmeat consumption and sale, suggests that such spillover events can occur.…”

Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

“…For example, we have designed other reporter-expressing viruses with their own unique advantages for in vivo studies, such as an NiV with a secreted Gaussia luciferase-P2A-EGFP dual-expression cassette that can be used to monitor viral load directly in tissues by bioluminescence imaging or indirectly by measuring Gaussia luciferase activity in serum (11). Future in vivo studies with these reporter constructs and recombinant henipavirus chimeras will not only reveal insights into NiV and HeV pathogenesis but also open the door to similar investigations into different NiV strains (e.g., the Malaysian strain versus the more diverse Bangladeshi strains, which also appear to differ significantly in both epidemiological and experimental contexts [50][51][52]) and newly discovered henipaviruses (such as Cedar virus and the African bat henipavirus Gh-M74a [4,5]).…”

“…In the past 2 years, examination of bats within and beyond the Pteropus genus has uncovered a multitude of previously undescribed henipaviruses of unknown virulence and implications for human health (4)(5)(6)(7). The more widespread prevalence of henipaviruses and the documented human-to-human transmission of some strains (8)(9)(10), along with recent evidence of potential henipavirus-like spillover events in Africa (11), suggest that increased global surveillance efforts directed at detecting henipavirus spillover events are warranted. Indeed, pandemic potential has been proposed for NiV (12).…”