ABSTRACT
A serological survey of 2,430 archived serum samples collected between 1997 and 2012 was conducted to retrospectively determine the prevalence of Marburg virus in five African countries. Serum samples were screened for neutralizing antibodies in a pseudotype micro-neutralization assay and confirmed by enzyme-linked immunosorbent assay (ELISA). Surprisingly, a seroprevalence for Marburg virus of 7.5 and 6.3% was found in Cameroon and Ghana, respectively, suggesting the circulation of filoviruses or related viruses outside of known endemic areas that remain undetected by current surveillance efforts. However, due to the lack of validated assays and appropriate positive controls, these results must be considered preliminary.
Subject(s)
Antibodies, Viral/blood , Filoviridae/immunology , Marburg Virus Disease/blood , Marburg Virus Disease/epidemiology , Marburgvirus/immunology , Animals , Cameroon/epidemiology , Enzyme-Linked Immunosorbent Assay , Filoviridae/genetics , Filoviridae Infections/blood , Filoviridae Infections/epidemiology , Filoviridae Infections/virology , Ghana/epidemiology , Humans , Marburg Virus Disease/virology , Marburgvirus/genetics , Retrospective Studies , Seroepidemiologic StudiesABSTRACT
With the exception of Reston and Bombali viruses, the marburgviruses and ebolaviruses (family Filoviridae) cause outbreaks of viral hemorrhagic fever in sub-Saharan Africa. The Egyptian rousette bat (ERB) is a natural reservoir host for the marburgviruses and evidence suggests that bats are also natural reservoirs for the ebolaviruses. Although the search for the natural reservoirs of the ebolaviruses has largely involved serosurveillance of the bat population, there are no validated serological assays to screen bat sera for ebolavirus-specific IgG antibodies. Here, we generate filovirus-specific antisera by prime-boost immunization of groups of captive ERBs with all seven known culturable filoviruses. After validating a system of filovirus-specific indirect ELISAs utilizing infectious-based virus antigens for detection of virus-specific IgG antibodies from bat sera, we assess the level of serological cross-reactivity between the virus-specific antisera and heterologous filovirus antigens. This data is then used to generate a filovirus antibody fingerprint that can predict which of the filovirus species in the system is most antigenically similar to the species responsible for past infection. Our filovirus IgG indirect ELISA system will be a critical tool for identifying bat species with high ebolavirus seroprevalence rates to target for longitudinal studies aimed at establishing natural reservoir host-ebolavirus relationships.
Subject(s)
Filoviridae Infections/immunology , Filoviridae/immunology , Age Factors , Animals , Antibodies, Viral/immunology , Antigens, Viral/immunology , Chiroptera/virology , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Female , Filoviridae/pathogenicity , Filoviridae Infections/blood , Immune Sera , Male , Viral Proteins/chemistry , Viral Proteins/immunologyABSTRACT
Filoviruses such as Ebola virus (EBOV), Marburg virus (MARV), and Sudan virus (SUDV) cause deadly viral hemorrhagic fever in humans, with high case-fatality rates; however, no licensed therapeutic agent or vaccine has been clinically approved to treat or prevent infection. T-705 (favipiravir) is a novel antiviral drug that has been approved for the treatment of influenza in Japan. T-705 exhibits broad-spectrum antiviral activity against different viruses, including MARV and EBOV, and here, we are the first to report the in vitro and in vivo antiviral activity of T-705 against SUDV. T-705 treatment reduced SUDV replication in Vero E6 cells. Subcutaneous administration of T-705, beginning 1-4 days after infection and continuing for 7 days, significantly protected SUDV-infected guinea pigs, with a survival rate of 83%-100%. Viral RNA replication and infectious virus production were also significantly reduced in the blood, spleen, liver, lungs, and kidney. Moreover, early administration of low-dose T-705 and late administration (at 5 days after infection) of higher-dose T-705 also showed partial protection. Overall, our study is the first to demonstrate the antiviral activity of T-705 against SUDV, suggesting that T-705 may be a potential drug candidate for use during outbreaks.
Subject(s)
Amides/therapeutic use , Antiviral Agents/therapeutic use , Filoviridae Infections/prevention & control , Pyrazines/therapeutic use , Animals , Blood Cell Count , Chlorocebus aethiops , Female , Filoviridae Infections/blood , Filoviridae Infections/virology , Guinea Pigs , RNA, Viral/analysis , Vero Cells , Virus Replication/drug effectsABSTRACT
Bats are suspected to play important roles in the ecology of filoviruses, including ebolaviruses and marburgviruses. A cave-dwelling fruit bat, Rousettus aegyptiacus, has been shown to be a reservoir of marburgviruses. Using an enzyme-linked immunosorbent assay with the viral glycoprotein antigen, we detected immunoglobulin G antibodies specific to multiple filoviruses in 158 of 290 serum samples of R aegyptiacus bats captured in Zambia during the years 2014-2017. In particular, 43.8% of the bats were seropositive to marburgvirus, supporting the notion that this bat species continuously maintains marburgviruses as a reservoir. Of note, distinct peaks of seropositive rates were repeatedly observed at the beginning of rainy seasons, suggesting seasonality of the presence of newly infected individuals in this bat population. These data highlight the need for continued monitoring of filovirus infection in this bat species even in countries where filovirus diseases have not been reported.
Subject(s)
Chiroptera/blood , Chiroptera/immunology , Filoviridae Infections/blood , Filoviridae Infections/immunology , Filoviridae/immunology , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Chiroptera/virology , Disease Reservoirs/virology , Female , Filoviridae Infections/virology , Glycoproteins/blood , Glycoproteins/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Seroepidemiologic Studies , ZambiaABSTRACT
Fruit bats are suspected to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Using an enzyme-linked immunosorbent assay based on the viral glycoprotein antigens, we detected filovirus-specific immunoglobulin G antibodies in 71 of 748 serum samples collected from migratory fruit bats (Eidolon helvum) in Zambia during 2006-2013. Although antibodies to African filoviruses (eg, Zaire ebolavirus) were most prevalent, some serum samples showed distinct specificity for Reston ebolavirus, which that has thus far been found only in Asia. Interestingly, the transition of filovirus species causing outbreaks in Central and West Africa during 2005-2014 seemed to be synchronized with the change of the serologically dominant virus species in these bats. These data suggest the introduction of multiple species of filoviruses in the migratory bat population and point to the need for continued surveillance of filovirus infection of wild animals in sub-Saharan Africa, including hitherto nonendemic countries.
Subject(s)
Chiroptera/virology , Filoviridae Infections/epidemiology , Filoviridae Infections/virology , Filoviridae/immunology , Africa/epidemiology , Animals , Antibodies, Viral/blood , Asia/epidemiology , Cell Line , Chiroptera/blood , Chiroptera/immunology , Disease Outbreaks , Ebolavirus/immunology , Female , Filoviridae Infections/blood , Filoviridae Infections/immunology , Glycoproteins/immunology , HEK293 Cells , Hemorrhagic Fever, Ebola/blood , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/virology , Humans , Immunoglobulin G/blood , Male , Prevalence , Viral Proteins/immunologyABSTRACT
Filoviruses are responsible for highly lethal infections. Those viruses are found in intertropical areas of Africa and Asia where they circulate in their supposed natural reservoir, fruit bats. During filovirus outbreaks and depending on the strains, various modifications in hemostasis have been observed in patients. The disseminated intravascular coagulation identified in these infections is multicausal and involves both viral factors and abnormal physiological responses. In this review we will describe the mechanisms responsible for these disturbances and we will highlight some aspects of the basis of filovirus high pathogenicity.
Subject(s)
Disseminated Intravascular Coagulation/etiology , Filoviridae Infections/blood , Adrenal Cortex/pathology , Animals , Chiroptera/virology , Communicable Diseases, Emerging/blood , Communicable Diseases, Emerging/complications , Cytokines/metabolism , Disease Reservoirs , Endothelial Cells/pathology , Filoviridae/physiology , Filoviridae Infections/epidemiology , Filoviridae Infections/pathology , Filoviridae Infections/veterinary , Filoviridae Infections/virology , Haplorhini , Hepatocytes/pathology , Host-Pathogen Interactions , Humans , Necrosis , Recombinant Proteins/pharmacology , Recombinant Proteins/therapeutic use , Thromboplastin/antagonists & inhibitors , Thromboplastin/physiology , Viral Load , Viral Proteins/physiologySubject(s)
Filoviridae Infections/pathology , Animals , Capillary Permeability , Filoviridae Infections/blood , Filoviridae Infections/immunology , Guinea Pigs , Haplorhini , Hemostasis , Immune System/pathology , Kidney/pathology , Liver/pathology , Mice , Rats , Species Specificity , Spleen/pathologyABSTRACT
Filovirus infections in humans and primates cause intrinsic activation of the clotting cascade. Tissue factor, the normal activator of the clotting cascade, is released into the bloodstream from activated leukocytes and viral budding from infected cells. This release of tissue factor, a trans-membrane protein found in large amounts in cells preferred by filoviruses for replication, initiates the hemorrhagic complications characteristic of filovirus infection. These complications contribute to the high mortality rates of filovirus infections. Directing chemotheraputic measures at the release of tissue factor, which causes the hemorrhagic complications, will result in significant reductions of mortality rates in man and primates.