Serological prevalence of viral hemorrhagic fevers in Equatorial Africa

Vitalant, San Francisco CA

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Abstract

DESCRIPTION (provided by applicant): Viral hemorrhagic fevers (VHF) describe a diverse group of often-fatal illnesses accompanied by severe bleeding. All known VHF are caused by viruses from four distinct families of lipid- enveloped viruses, including the filoviruses (ebolavius and marburgvirus), arenaviruses (e.g. Lassa virus), bunyaviruses, and flaviviruses. The rhabdovirus Bas-Congo virus (BASV) was first identified by deep sequencing of nucleic acids extracted from a serum sample obtained from a patient with hemorrhagic fever in the Democratic Republic of Congo (DRC). Prior to falling ill, the mentioned patient was a caregiver for two adolescents from the same village who succumbed to a severe disease with similar symptoms, including hemorrhage. A vesicular stomatitis virus (VSV)-based pseudotype system enables us to test serum samples for the presence of antibodies that neutralize pseudoviruses bearing the BASV glycoprotein (BASV-G). A serum sample obtained from the initial patient almost 3 years after recovering from the disease revealed strong neutralization activity specific for BASV-G pseudotypes. Surprisingly, an asymptomatic close contact of the patient tested positive for BASV-G neutralizing antibodies with even higher titers, whereas other health care workers from the village did not show signs of exposure to BASV. Testing of 50 sera from blood donors identified one individual with moderate neutralizing activity specific to BASV-G. A key step in estimating the level of human exposure to BASV will be the screening of large numbers of serum samples from the area and surrounding countries for the presence of antibodies to BASV. The pseudotype neutralization assay is suitable for high-throughput processing of large sample numbers. However, it will exclusively detect antibodies targeting the viral glycoprotein, thereby interfering with infection of target cells. Consequentially, we confirm positivity with additional assays for other viral proteins, such as M and N. We plan to screen over 8000 sera from a total of seven countries for serological evidence of BASV infection, as well as looking at the basal seroprevalence of three additional VHFs - ebolavirus, marburgvirus and Lassa virus, as well as an additional African rhabdovirus, Kotonkan that is believed to infect humans, but is not thought to be a VHF.