Sand Fly–Associated Phlebovirus with Evidence of Neutralizing Antibodies in Humans, Kenya

Abstract

We describe a novel virus, designated Ntepes virus (NPV), isolated from sand flies in Kenya. NPV has the characteristic phlebovirus trisegmented genome architecture and is related to, but distinct from, Gabek Forest phlebovirus. Diverse cell cultures derived from wildlife, livestock, and humans were susceptible to NPV, with pronounced permissiveness in swine and rodent cells. NPV infection of newborn mice caused rapid and fatal illness. Permissiveness for NPV replication in sand fly cells, but not mosquito cells, suggests a vector-specific adaptation. Specific neutralizing antibodies were found in 13.9% (26/187) of human serum samples taken at the site of isolation of NPV as well as a disparate site in northeastern Kenya, suggesting a wide distribution. We identify a novel human-infecting arbovirus and highlight the importance of rural areas in tropical Africa for arbovirus surveillance as well as extending arbovirus surveillance to include hematophagous arthropods other than mosquitoes.

Insights into the Evolutionary Origin of Mediterranean Sandfly Fever Viruses

“…4). The NPV strain grouped with the previously detected NPV strain (19). Further analyses based on either the Gn, Gc, and N nucleotide or protein sequences of the novel viruses and their closest relatives confirmed the findings obtained for the RdRp-based trees (Fig.…”

“…Species of sandflies of the genus Sergentomyia have been suggested to be involved in the transmission of NPV (19). Our present study confirms that the Sergentomyia sandflies might be associated with NPV.…”

“…The viruses are distantly related to the medically important sandfly fever Sicilian serocomplex (BGRV, EMBV, and PERV), sandfly fever Naples serocomplex (KBGV), and Karimabad serocomplex (NPV), indicating the circulation of taxonomically highly diverse sandfly-borne phleboviruses in Kenya. We recently described the discovery and isolation of NPV from sandflies collected in Ntepes village, Marigat district, in 2014 (19). The repeated detection of NPV in sandflies originating from the same geographic area 2 years after the initial detection, together with our previous findings on the presence of neutralizing antibodies against NPV in humans from different regions in Kenya, provides further evidence that the virus is endemic and widely circulating in the country.…”

“…In addition, the entire CDS of NPV was directly sequenced from the sandfly homogenate and compared to the strain initially sequenced from infectious cell culture supernatant originating from sandflies collected in the same geographic region in 2014 (19). For the RdRp, GPC, N, and NSs genes, 15, 13, 2, and 4 synonymous substitutions, respectively, were detected between the two strains.…”

“…We recently detected a previously unknown phlebovirus termed Ntepes virus (NPV) in sandflies from Kenya ( 19 ). Neutralizing antibodies against NPV were found in humans in two distant geographic areas (>600 km apart) in Kenya, suggesting a wider distribution of the virus.…”