Serological prevalence of viral hemorrhagic fevers in Equatorial Africa

赤道非洲病毒性出血热的血清学流行情况

基本信息

批准号：
8698969
负责人：
GRAHAM SIMMONS
金额：
$ 24.65万
依托单位：
VITALANT
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8698969
关键词：
Acute Adolescent Africa African Antibodies Antigens Area Arenavirus Biological Assay Blood donor Cameroon Caregivers Cells Clinical Country Crimean Hemorrhagic Fever Crimean-Congo Hemorrhagic Fever Virus Democratic Republic of the Congo Disease Disease Outbreaks Ebola virus Enzyme-Linked Immunosorbent Assay Event Exposure to Family Filovirus Flavivirus Frankfurt-Marburg Syndrome Virus General Population Glycoproteins Health Personnel Hemorrhage Human Individual Infection Lassa virus Learning Link Lipids Nucleic Acids Orthobunyavirus Patients Penetrance Plasma Population Prevalence Process Rattus Recombinants Reverse Transcriptase Polymerase Chain Reaction Rhabdoviridae Sampling Serological Seroprevalences Serum South American Surveys Symptoms System Technology Testing Time Togo Uganda Vesicular stomatitis Indiana virus Viral Viral Hemorrhagic Fevers Viral Proteins Virus Weather Western Blotting Work base deep sequencing exposed human population falls glycoprotein G hemorrhagic fever virus high throughput screening indexing internal control neutralizing antibody nonhuman primate novel public health relevance repository research study screening transmission process vector viral RNA

项目摘要

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.

描述（由申请人提供）：病毒出血发烧（VHF）描述了一组经常致命的疾病，并伴有严重的出血。所有已知的VHF均由四个不同的脂质包蛋白病毒家族的病毒引起，包括丝状病毒（埃博拉维乌斯和马堡病毒），体育症病毒（例如LASSA病毒），Bunyaviruses和Flaviviruses。首先通过从刚果民主共和国（DRC）中从患有出血热的患者获得的血清样本中提取的核酸进行深度测序，首先鉴定出黄褐病毒bas-congo病毒（BASV）。在生病之前，提到的患者是同一个村庄的两个青少年的照料者，他们屈服于患有类似症状的严重疾病，包括出血。基于囊泡的口腔炎病毒（VSV）的假型系统使我们能够测试血清样品是否存在中和带有BASV糖蛋白（BASV-G）的伪病毒的抗体。从疾病中恢复后，从初始患者获得的血清样品显示出对BASV-G假型特有的强中和活性。令人惊讶的是，患者的无症状紧密接触对BASV-G中和抗体的阳性呈阳性，而较高的滴度则呈较高的滴度，而来自村庄的其他医疗保健工作者并未显示出暴露于BASV的迹象。对血液供体的50种血清的测试确定了一个特定于BASV-G的中和活性中和中和的人。估计人类接触BASV水平的关键步骤是筛选来自该地区和周边国家的大量血清样品，以供抗体与BASV抗体。假型中和测定适用于大型样本数量的高通量处理。但是，它将仅检测靶向病毒糖蛋白的抗体，从而干扰靶细胞的感染。 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感染人类，但被认为不是VHF。