Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa

Abstract

Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.

The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus)

“…Pegivirus C (GBV-C or HPegV-1), an RNA virus in the genus Flavivirus, was the second most common viral nucleic acid detected in this study and was also commonly detected in a study of both healthy and febrile Nigerians (Stremlau et al, 2015). In contrast, this virus was rarely detected in a study of febrile Nicaraguan children (Yozwiak et al, 2012).…”

“…These have been Lassa virus [in southeast Nigerian patients of all ages (Stremlau et al, 2015)], HHV-6 [in DENV-negative children from Nicaragua (Yozwiak et al, 2012)], and parvovirus B19 in this study. Such differences may reflect regional or temporal variation in the major viral causes of fever other than DENV, the inclusion of patients from different age groups, or methodological differences in the generation of viral sequences.…”

“…The next most commonly detected infections in this study were the three known species of human anelloviruses, another group of ssDNA viruses. Anelloviruses were not reported in the Nigerian study, which focused on RNA viruses (Stremlau et al, 2015), but were the most commonly detected viruses in the study of Nicaraguan children (Yozwiak et al, 2012). Anellovirus infection is nearly universal, acquired early in life, often results in chronic viraemia, and frequently involves multiple species and genotypes (Bernardin et al, 2010).…”

“…A prior study analysing a febrile population in southeast Nigeria did not report parvovirus B19 detection, likely due to its focus on RNA viruses (Stremlau et al, 2015). Typically transmitted by the respiratory route, parvovirus B19 can cause fever and an evanescent rash (fifth disease) in otherwise healthy children (Rogo et al, 2014).…”

“…Using C6/ 36 cells, the virus was also isolated from mosquitoes from Northwest Yunnan province in China (Sun et al, 2009). To date, Kadipiro virus has not been reported to be amplified in mammalian cell lines or recovered following mice inoculations.…”