4.7 Article

Profile and Persistence of the Virus-Specific Neutralizing Humoral Immune Response in Human Survivors of Sudan Ebolavirus (Gulu)

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 208, Issue 2, Pages 299-+

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit162

Keywords

ebolavirus; immune response; epitopes; antibodies; sera screening; serological profiling

Funding

  1. National Institute of Biotechnology in the Negev, Beersheva, Israel
  2. Feldman Family Foundation

Ask authors/readers for more resources

To better understand humoral immunity following ebolavirus infection, a serological study of the humoral immune response against the individual viral proteins of Sudan ebolavirus (Gulu) in human survivors was performed. An enzyme-linked immunosorbent assay specific for full-length recombinant viral proteins NP, VP30, VP40, and GP(1-649) (GP lacking the transmembrane domain) of Sudan ebolavirus (Gulu) was used as well as a plaque reduction neutralization test. Serum samples from human survivors, which were collected up to 10 years following recovery, were screened and analyzed. Results demonstrate that samples obtained 10 years following infection contain virus-specific antibodies that can neutralize virus. Neutralization correlates well with immunoreactivity against the viral proteins NP, VP30, and GP(1-649). Sera from individuals who died or those with no documented infection but immunoreactive to ebolavirus did not neutralize. This work provides insight into the duration, profile of immunoreactivity, and neutralization capacity of the humoral immune response in ebolavirus survivors.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Immunology

HIV infection drives pro-inflammatory immunothrombotic pathway activation and organ dysfunction among adults with sepsis in Uganda

Matthew J. Cummings, Barnabas Bakamutumaho, Adam Price, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Komal Jain, Thomas S. Postler, Moses Muwanga, Christopher Nsereko, Irene Nayiga, Stephen Kyebambe, Xiaoyu Che, Stephen Sameroff, Rafal Tokarz, Shivang S. Shah, Michelle H. Larsen, W. Ian Lipkin, Julius J. Lutwama, Max R. O'Donnell

Summary: This study investigated the influence of HIV infection on the immunopathology and organ dysfunction of patients hospitalized with suspected sepsis in Uganda. The results showed that HIV-infected patients presented with more severe physiological disturbances and shock, and had a higher mortality rate at 30 days. Furthermore, HIV-infected patients exhibited exaggerated activation of multiple immune and thrombotic metabolic pathways. This study revealed the specific circumstances of HIV-infected patients in the pathogenesis of sepsis, providing important information for further research and treatment.
Article Public, Environmental & Occupational Health

Development of a Novel Clinicomolecular Risk Index to Enhance Mortality Prediction and Immunological Stratification of Adults Hospitalized with Sepsis in Sub-Saharan Africa: A Pilot Study from Uganda

Matthew J. Cummings, Barnabas Bakamutumaho, Komal Jain, Adam Price, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Moses Muwanga, Christopher Nsereko, Stephen Sameroff, W. Ian Lipkin, Julius J. Lutwama, Max R. O'Donnell

Summary: The global burden of sepsis is particularly severe in sub-Saharan Africa (SSA), where the management of severe infections is challenged by epidemic HIV and unique pathogen diversity. In a prospective cohort study in Uganda, machine learning methods were used to develop a prediction model for 30-day mortality in adults with suspected sepsis. The model integrated physiology-based risk scores with soluble biomarkers and showed enhanced prediction accuracy when combined with whole-blood RNA sequencing data.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2023)

Article Public, Environmental & Occupational Health

Phylogenetic Analysis of Wesselsbron Virus Isolated from Field-Captured Mosquitoes during a Rift Valley Fever Outbreak in Kabale District, Uganda-2016

John T. Kayiwa, Martin N. Mayanja, Teddy Muwawu Nakayiki, Fred Senfuka, Julius Mugga, Jeffrey W. Koehler, Eric C. Mossel, Julius J. Lutwama

Summary: In response to two human cases of Rift Valley fever (RVF) in Uganda, an entomological investigation was carried out to determine the mosquito species and abundance, identify potential mosquito vectors, and test for virus transmission. The study revealed the isolation of two Wesselsbron virus strains, a neglected arbovirus, from Aedes tricholabis and Ae. gibbinsi mosquitoes. These isolates represent the first reported Wesselsbron virus strains in Uganda since 1966.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2023)

Article Immunology

Brief Report: Detection of Urine Lipoarabinomannan Is Associated With Proinflammatory Innate Immune Activation, Impaired Host Defense, and Organ Dysfunction in Adults With Severe HIV-Associated Tuberculosis in Uganda

Matthew J. Cummings, Barnabas Bakamutumaho, Komal Jain, Adam Price, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Moses Muwanga, Christopher Nsereko, Irene Nayiga, Stephen Kyebambe, Xiaoyu Che, Stephen Sameroff, Rafal Tokarz, Wai Wong, Thomas S. Postler, Michelle H. Larsen, W. Ian Lipkin, Julius J. Lutwama, Max R. O'Donnell

Summary: This study found that detection of urine TB-LAM was associated with organ dysfunction and immune responses in hospitalized adults with severe HIV/TB. Higher TB-LAM grade was correlated with more severe physiological derangement and impaired antibacterial defense. Therefore, immunomodulatory therapies may be a potential strategy for treating critically ill HIV/TB patients.

JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES (2023)

Article Microbiology

A dsRNA-binding mutant reveals only a minor role of exonuclease activity in interferon antagonism by the arenavirus nucleoprotein

Patrick Bohn, Irke Wassmann, Lisa Wendt, Anne Leske, Thomas Hoenen, Birke A. Tews, Allison Groseth

Summary: This study demonstrates that a specific mutation can accurately assess the role of a protein in viral antagonism of interferon production. The mutation inhibits the protein's exonuclease activity while still efficiently blocking interferon production.

PLOS PATHOGENS (2023)

Article Infectious Diseases

No Evidence of Ntwetwe Virus Infections in Children Presenting to Kiboga Hospital, Uganda

Arthur W. D. Edridge, Nathalie van den Brekel, Philly Mukungu, Rachael Nakayima, Samuel Bbosa, Peter Isagara, Michael Boele van Hensbroek, Lia van der Hoek, John Kayiwa, Julius J. Lutwama, Richard Idro

Summary: We investigated whether a novel orthobunyavirus called Ntwetwe virus, which was discovered in a Ugandan girl with a fatal encephalopathy, was a common cause of hospital admission for children to Kiboga hospital in Uganda. A case-control study was conducted between September 2019 and September 2020, comparing cases with severe neurological disease and mild febrile illness to healthy controls without fever. Among 143 subjects, no cases with an acute infection of Ntwetwe virus were identified. This suggests that Ntwetwe virus does not contribute significantly to the disease burden among children seeking medical care at Kiboga hospital during the study period.

TROPICAL MEDICINE AND INFECTIOUS DISEASE (2023)

Review Biochemistry & Molecular Biology

Conversations in the Gut: The Role of Quorum Sensing in Normobiosis

Victor Markus, Abraham Abbey Paul, Kerem Terali, Nazmi Ozer, Robert S. Marks, Karina Golberg, Ariel Kushmaro

Summary: An imbalance in gut microbiota, called dysbiosis, can affect host health and lead to diseases like inflammatory bowel disease, cancer, obesity, depression, and autism. The inhibition of bacterial quorum sensing (QS) by artificial sweeteners has been found to contribute to this dysbiosis. QS is a communication system mediated by small molecules, called autoinducers (AIs), which enable bacteria to interact and coordinate their gene expression. AIs play a role in maintaining the equilibrium of gut microbiota and interference in QS can disrupt this balance.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

Article Infectious Diseases

Immunocompetent hamsters as a model for orthobunyavirus-induced neuroinvasion and neuropathology

Allison Groseth, Don Gardner, Kimberly Meade-White, Susanne Amler, Hideki Ebihara

Summary: Researchers have developed a new hamster model for studying bunyavirus infection, which provides a more authentic cellular and immunological context at the initial site of infection. This model helps to investigate the mechanisms of neuroinvasion and neuropathology and can be used for testing antiviral approaches targeting bunyaviruses.

PLOS NEGLECTED TROPICAL DISEASES (2023)

Article Immunology

N6-methyladenosine is required for efficient RNA synthesis of Ebola virus and other haemorrhagic fever viruses

Lisa Wendt, Matthew J. Pickin, Bianca S. Bodmer, Sven Reiche, Lucie Feneant, Julia E. Hoelper, Walter Fuchs, Allison Groseth, Thomas Hoenen

Summary: By analyzing the m(6)A methylation pattern of hemorrhagic fever viruses, it was found that METTL3 interacts with their nucleoproteins and transcriptional activators to support viral RNA synthesis. This interaction and its importance for RNA synthesis and protein expression were also observed in other hemorrhagic fever viruses. Loss of m(6)A methylation had negative effects on viral RNA synthesis, independent of innate immune sensing.

EMERGING MICROBES & INFECTIONS (2023)

Article Infectious Diseases

3,3′-Diindolylmethane (DIM): A Potential Therapeutic Agent against Cariogenic Streptococcus mutans Biofilm

Yifat Baruch, Karina Golberg, Qun Sun, Karina Yew-Hoong Gin, Robert S. Marks, Ariel Kushmaro

Summary: This study tested the effect of a natural compound called 3,3'-Diindolylmethane (DIM) on the biofilm of the oral bacterium Streptococcus mutans. The results showed that DIM was able to reduce the formation of S. mutans biofilm and decrease its durability under acidic conditions. This suggests that DIM has potential in reducing biofilm formation and preventing dental caries.

ANTIBIOTICS-BASEL (2023)

Article Virology

The Rise and Fall of Omicron BA.1 Variant as Seen in Wastewater Supports Epidemiological Model Predictions

Michal Liddor Naim, Yu Fu, Marilou Shagan, Itay Bar-Or, Robert Marks, Qun Sun, Rony Granek, Ariel Kushmaro

Summary: The COVID-19 pandemic has caused significant mortality and morbidity worldwide. Continuous virus mutations have led to the emergence of new variants. This study demonstrates the potential of wastewater-based epidemiology as a valuable tool for future pandemics, as it enables early detection of potential outbreaks and provides insights into variant dynamics.

VIRUSES-BASEL (2023)

Article Immunology

Crimean-Congo Hemorrhagic Fever Outbreak in Refugee Settlement during COVID-19 Pandemic, Uganda, April 2021

Luke Nyakarahuka, Shannon Whitmer, Jackson Kyondo, Sophia Mulei, Caitlin M. Cossaboom, Carson T. Telford, Alex Tumusiime, Gloria Grace Akurut, Dianah Namanya, Kilama Kamugisha, Jimmy Baluku, Julius Lutwama, Stephen Balinandi, Trevor Shoemaker, John D. Klena

Summary: Two cases of Crimean-Congo hemorrhagic fever (CCHF) were detected among refugees in a settlement in Kikuube district, Uganda. Further investigations revealed a high prevalence of CCHF IgG antibodies (71.3%) in goats within the settlement. This highlights the importance of a multi-sectoral approach to controlling CCHF in both humans and animals in Uganda.

EMERGING INFECTIOUS DISEASES (2022)

Article Immunology

Rift Valley Fever Outbreak during COVID-19 Surge, Uganda, 2021

Caitlin M. Cossaboom, Luke Nyakarahuka, Sophia Mulei, Jackson Kyondo, Alex Tumusiime, Jimmy Baluku, Gloria Grace Akurut, Dianah Namanya, Kilama Kamugisha, Hildah Tendo Nansikombi, Alex Nyabakira, Semei Mutesasira, Shannon Whitmer, Carson Telford, Julius Lutwama, Stephen Balinandi, Joel Montgomery, John D. Klena, Trevor Shoemaker

Summary: Seven confirmed Rift Valley fever cases, including one fatality, were reported in Kiruhura District, Uganda in 2021. Our findings underscore the importance of ongoing surveillance for viral hemorrhagic fevers, despite the challenges posed by the COVID-19 pandemic.

EMERGING INFECTIOUS DISEASES (2022)

Article Immunology

Rapid Replacement of SARS-CoV-2 Variants by Delta and Subsequent Arrival of Omicron, Uganda, 2021

Nicholas Bbosa, Deogratius Ssemwanga, Hamidah Namagembe, Ronald Kiiza, Jocelyn Kiconco, John Kayiwa, Tom Lutalo, Julius Lutwama, Alfred Ssekagiri, Isaac Ssewanyana, Susan Nabadda, Henry Kyobe-Bbosa, Jennifer Giandhari, Sureshnee Pillay, Upasana Ramphal, Yajna Ramphal, Yeshnee Naidoo, Derek Tshiabuila, Houriiyah Tegally, Emmanuel J. San, Eduan Wilkinson, Tulio de Oliveira, Pontiano Kaleebu

Summary: Genomic surveillance in Uganda has shown the rapid replacement of severe acute respiratory syndrome coronavirus 2 variants over time, with Delta dominating. However, the detection of the more transmissible Omicron variant among travelers and increasing community transmission emphasize the importance of near-real-time genomic surveillance and adherence to infection control measures in preventing future pandemic waves.

EMERGING INFECTIOUS DISEASES (2022)

Article Critical Care Medicine

Multidimensional analysis of the host response reveals prognostic and pathogen-driven immune subtypes among adults with sepsis in Uganda

Matthew J. Cummings, Barnabas Bakamutumaho, Adam Price, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Moses Muwanga, Christopher Nsereko, Stephen Sameroff, Rafal Tokarz, Wai Wong, Shivang S. Shah, Michelle H. Larsen, W. Ian Lipkin, Julius J. Lutwama, Max R. O'Donnell

Summary: This study identified two immune subtypes among 288 adults hospitalized with sepsis in Uganda, characterized by differential activation of pro-inflammatory innate and adaptive immune pathways, T-cell exhaustion, metabolic reprogramming, and association with severe HIV-associated tuberculosis, extensive organ dysfunction, worse functional outcomes, and higher 30-day mortality. These results emphasize the unique features of sepsis immunopathology in sub-Saharan Africa and highlight the importance of developing more biologically-informed treatment strategies incorporating immunomodulation in the region.

CRITICAL CARE (2022)

No Data Available