A near full-length #HIV-1 #genome from 1966 recovered from #formalin-fixed paraffin-embedded #tissue (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

A near full-length HIV-1 genome from 1966 recovered from formalin-fixed paraffin-embedded tissue

Sophie Gryseels, Thomas D. Watts, Jean-Marie Kabongo Mpolesha, Brendan B. Larsen, Philippe Lemey, Jean-Jacques Muyembe-Tamfum, Dirk E. Teuwen, and Michael Worobey

PNAS first published May 19, 2020 https://doi.org/10.1073/pnas.1913682117

Edited by Beatrice H. Hahn, University of Pennsylvania, Philadelphia, PA, and approved April 6, 2020 (received for review August 16, 2019)

 

Significance

Inferring the precise timing of the origin of the HIV/AIDS pandemic is of great importance because it offers insights into which factors did—or did not—facilitate the emergence of the causal virus. Previous estimates have implicated rapid development during the early 20th century in Central Africa, which wove once-isolated populations into a more continuous fabric. We recovered the first HIV-1 genome from the 1960s, and it provides direct evidence that HIV-1 molecular clock estimates spanning the last half-century are remarkably reliable. And, because this genome itself was sampled only about a half century after the estimated origin of the pandemic, it empirically anchors this crucial inference with high confidence.

 

Abstract

With very little direct biological data of HIV-1 from before the 1980s, far-reaching evolutionary and epidemiological inferences regarding the long prediscovery phase of this pandemic are based on extrapolations by phylodynamic models of HIV-1 genomic sequences gathered mostly over recent decades. Here, using a very sensitive multiplex RT-PCR assay, we screened 1,645 formalin-fixed paraffin-embedded tissue specimens collected for pathology diagnostics in Central Africa between 1958 and 1966. We report the near-complete viral genome in one HIV-1 positive specimen from Kinshasa, Democratic Republic of Congo (DRC), from 1966 (“DRC66”)—a nonrecombinant sister lineage to subtype C that constitutes the oldest HIV-1 near full-length genome recovered to date. Root-to-tip plots showed the DRC66 sequence is not an outlier as would be expected if dating estimates from more recent genomes were systematically biased; and inclusion of the DRC66 sequence in tip-dated BEAST analyses did not significantly alter root and internal node age estimates based on post-1978 HIV-1 sequences. There was larger variation in divergence time estimates among datasets that were subsamples of the available HIV-1 genomes from 1978 to 2014, showing the inherent phylogenetic stochasticity across subsets of the real HIV-1 diversity. Our phylogenetic analyses date the origin of the pandemic lineage of HIV-1 to a time period around the turn of the 20th century (1881 to 1918). In conclusion, this unique archival HIV-1 sequence provides direct genomic insight into HIV-1 in 1960s DRC, and, as an ancient-DNA calibrator, it validates our understanding of HIV-1 evolutionary history.

HIV-1 – evolution – virus – phylogeny

 

Footnotes

1 To whom correspondence may be addressed. Email: worobey@email.arizona.edu.

Author contributions: M.W. designed research; S.G., T.D.W., and M.W. performed research; J.-M.K.M., J.-J.M.-T., and D.E.T. contributed new reagents/analytic tools; S.G., T.D.W., B.B.L., P.L., and M.W. analyzed data; and S.G. and M.W. wrote the paper.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

Data deposition: The DRC66 genome sequence is deposited in GenBank with accession number MN082768. Alignments and BEAST xml files are available at https://github.com/sophiegryseels/DRC66.

This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1913682117/-/DCSupplemental.

Published under the PNAS license.

Keywords: HIV/AIDS; DRC; Genetics; Evolution.

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#Molecular, #antigenic, and #pathogenic characterization of #H5N8 highly pathogenic #avian #influenza viruses isolated in the #DRC in 2017 (Arch Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Arch Virol. 2020 Jan;165(1):87-96. doi: 10.1007/s00705-019-04456-x. Epub 2019 Nov 9.

Molecular, antigenic, and pathogenic characterization of H5N8 highly pathogenic avian influenza viruses isolated in the Democratic Republic of Congo in 2017.

Twabela AT1,2, Okamatsu M1, Tshilenge GM2, Mpiana S2, Masumu J2, Nguyen LT1, Matsuno K1,3, Monne I4, Zecchin B4, Sakoda Y5,6.

Author information: 1 Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan. 2 Central Veterinary Laboratory of Kinshasa, Kinshasa I, Gombe, Democratic Republic of Congo. 3 Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, Japan. 4 Istituto Zooprofilattico Sperimentale Delle Venezie, Legnaro, PD, Italy. 5 Laboratory of Microbiology, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, North 18, West 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan. sakoda@vetmed.hokudai.ac.jp. 6 Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Hokkaido, Japan. sakoda@vetmed.hokudai.ac.jp.

 

Abstract

In May 2017, high mortality of chickens and Muscovy ducks due to the H5N8 highly pathogenic avian influenza virus (HPAIV) was reported in the Democratic Republic of Congo (DR Congo). In this study, we assessed the molecular, antigenic, and pathogenic features in poultry of the H5N8 HPAIV from the 2017 Congolese outbreaks. Phylogenetic analysis of the eight viral gene segments revealed that all 12 DR Congo isolates clustered in clade 2.3.4.4B together with other H5N8 HPAIVs isolated in Africa and Eurasia, suggesting a possible common origin of these viruses. Antigenically, a slight difference was observed between the Congolese isolates and a representative virus from group C in the same clade. After intranasal inoculation with a representative DR Congo virus, high pathogenicity was observed in chickens and Muscovy ducks but not in Pekin ducks. Viral replication was higher in chickens than in Muscovy duck and Pekin duck organs; however, neurotropism was pronounced in Muscovy ducks. Our data confirmed the high pathogenicity of the DR Congo virus in chickens and Muscovy ducks, as observed in the field. National awareness and strengthening surveillance in the region are needed to better control HPAIVs.

PMID: 31707455 DOI: 10.1007/s00705-019-04456-x [Indexed for MEDLINE]

Keywords: Avian Influenza; H5N8; Poultry; DRC.

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Recurrent #Ebolavirus disease in the #DRC: #update and #challenges (AIMS Public Health, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

AIMS Public Health. 2019 Nov 20;6(4):502-513. doi: 10.3934/publichealth.2019.4.502. eCollection 2019.

Recurrent Ebolavirus disease in the Democratic Republic of Congo: update and challenges.

Inungu J1, Iheduru-Anderson K2, Odio OJ3.

Author information: 1 Master of Public Health Program, College of Health Professions, Central Michigan University, Michigan, United States. 2 Nursing Program, Central Michigan University, Michigan, United States. 3 Department of Internal Medicine, Medical School Hospital, University of Kinshasa, Kinshasa, Congo.

 

Abstract

The current Ebolavirus disease (EVD) outbreak in the provinces of North Kivu and Ituri is the tenth outbreak affecting the Democratic Republic of Congo (DRC); the first outbreak occurring in a war context, and the second most deadly Ebolavirus outbreak on record following the 2014 outbreak in West Africa. The DRC government’s response consisted of applying a package of interventions including detection and rapid isolation of cases, contact tracing, population mapping, and identification of high-risk areas to inform a coordinated effort. The coordinated effort was to screen, ring vaccinate, and conduct laboratory diagnoses using GeneXpert (Cepheid) polymerase chain reaction. The effort also included ensuring safe and dignified burials and promoting risk communication, community engagement, and social mobilization. Following the adoption of the “Monitored Emergency Use of Unregistered Products Protocol,” a randomized controlled trial of four investigational treatments (mAb114, ZMapp, and REGN-EB3 and Remdesivir) was carried out with all consenting patients with laboratory-confirmed EVD. REGN-EB3 and mAb114 showed promise as treatments for EVD. In addition, one investigational vaccine (rVSV-ZEBOV-GP) was used first, followed by a second prophylactic vaccine (Ad26.ZEBOV/MVA-BN-Filo) to reinforce the prevention. Although the provision of clinical supportive care remains the cornerstone of EVD outbreak management, the DRC response faced daunting challenges including general insecurity, violence and community resistance, appalling poverty, and entrenched distrust of authority. Ebolavirus remains a public health threat. A fully curative treatment is unlikely to be a game-changer given the settings of transmission, zoonotic nature, limits of effectiveness of any therapeutic intervention, and timing of presentation.

© 2019 the Author(s), licensee AIMS Press.

KEYWORDS: Ebola outbreak; epidemiology; hemorrhagic fever; prevention; treatment

PMID: 31909070 PMCID: PMC6940573 DOI: 10.3934/publichealth.2019.4.502

Keywords: Ebola; DRC; Public Health.

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Full-Length #Genome #Sequence of a #Dengue serotype 1 virus isolate from a #traveller returning from #DRC to #Italy, July 2019 (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2019 Dec 19. pii: S1201-9712(19)30496-5. doi: 10.1016/j.ijid.2019.12.023. [Epub ahead of print]

Full-Length Genome Sequence of a Dengue serotype 1 virus isolate from a traveller returning from Democratic Republic of Congo to Italy, July 2019.

Colavita F1, Vairo F2, Carletti F1, Boccardo C3, Ferraro F1, Iaiani G4, Al Moghazi S1, Galardo G3, Lalle E1, Selvaggi C1, Scognamiglio P1, Capobianchi MR1, Ippolito G1, Castilletti C1.

Author information: 1 National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ IRCCS, 00149 Rome, Italy. 2 National Institute for Infectious Diseases ‘Lazzaro Spallanzani’ IRCCS, 00149 Rome, Italy. Electronic address: francesco.vairo@inmi.it. 3 Dipartimento di Emergenza e Accettazione, Policlinico Umberto 1, Rome, Italy. 4 Dipartimento di Malattie Infettive e Tropicali, Policlinico Umberto 1, Rome, Italy.

 

Abstract

We report the full-genome sequence of a Dengue serotype-1 virus (DENV-1) isolated from a traveller returning in July 2019 to Italy from Democratic Republic of Congo (DRC), which is currently affected by Ebola and measles outbreaks. The sequence shows high similarity with two 2013 strains isolated in Angola and China.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Democratic Republic of Congo; Dengue virus; Full-genome sequence; Travel-associated infection

PMID: 31866548 DOI: 10.1016/j.ijid.2019.12.023

Keywords: Dengue fever; DRC; Italy.

——

A Randomized, Controlled #Trial of #Ebola Virus Disease #Therapeutics (N Engl J Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

N Engl J Med. 2019 Nov 27. doi: 10.1056/NEJMoa1910993. [Epub ahead of print]

A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.

Mulangu S1, Dodd LE1, Davey RT Jr1, Tshiani Mbaya O1, Proschan M1, Mukadi D1, Lusakibanza Manzo M1, Nzolo D1, Tshomba Oloma A1, Ibanda A1, Ali R1, Coulibaly S1, Levine AC1, Grais R1, Diaz J1, Lane HC1, Muyembe-Tamfum JJ1; PALM Writing Group; PALM Consortium Study Team, Sivahera B1, Camara M1, Kojan R1, Walker R1, Dighero-Kemp B1, Cao H1, Mukumbayi P1, Mbala-Kingebeni P1, Ahuka S1, Albert S1, Bonnett T1, Crozier I1, Duvenhage M1, Proffitt C1, Teitelbaum M1, Moench T1, Aboulhab J1, Barrett K1, Cahill K1, Cone K1, Eckes R1, Hensley L1, Herpin B1, Higgs E1, Ledgerwood J1, Pierson J1, Smolskis M1, Sow Y1, Tierney J1, Sivapalasingam S1, Holman W1, Gettinger N1, Vallée D1, Nordwall J1.

Author information: 1 From Institut National de Recherche Biomédicale, Democratic Republic of Congo (S.M., O.T.M., D.M., M.L.M., D.N., A.T.O., A.I., R.A., J.-J.M.-T.); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (L.E.D., R.T.D., M.P., H.C.L.); the Alliance for International Medical Action, Dakar, Senegal (S.C.); International Medical Corps, Los Angeles (A.C.L.); Epicentre, Médecins sans Frontières, Paris (R.G.); and the World Health Organization, Geneva (J.D.).The affiliations of the members of the PALM Writing Group are as follows: the Alliance for International Medical Action (B.S., M.C., R.K.); the Biomedical Advanced Research and Development Authority (R.W.); Battelle (B.D.-K.); Gilead (H.C.); Institut National de Recherche Biomédicale (P.M., P.M.-K., S. Ahuka); Leidos (S. Albert, T.B., I.C., M.D., C.P., M.T.); Mapp Biopharmaceutical (T.M.); the National Institute of Allergy and Infectious Diseases (J.A., K.B., K. Cahill, K. Cone, R.E., L.H., B.H., E.H., J.L., J.P., M.S., Y.S., J.T.); Regeneron (S.S.); Ridgeback Biotherapeutics (W.H.); the Mitchell Group (N.G., D.V.); and University of Minnesota (J.N.).

 

Abstract

BACKGROUND:

Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.

METHODS:

We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days.

RESULTS:

A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs.

CONCLUSIONS:

Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.).

Copyright © 2019 Massachusetts Medical Society.

PMID: 31774950 DOI: 10.1056/NEJMoa1910993

Keywords: Ebola; Antivirals; Remdesivir; Monoclonal antibodies; ZMapp; DRC.

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#Assessment of a #health #facility based active case #finding system for #Ebola virus disease in Mbandaka, #DRC, June-July 2018 (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2019 Nov 21;19(1):981. doi: 10.1186/s12879-019-4600-4.

Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June-July 2018.

Kunkel A1,2, Keita M3, Diallo B3, le Polain de Waroux O4,5,6,7, Subissi L8, Wague B4,9, Molala R10, Lonfandjo P10, Bokete SB10, Perea W11, Djingarey MH3.

Author information: 1 Emerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France. agkunkel@gmail.com. 2 Global Outbreak Alert and Response Network (GOARN), Geneva, Switzerland. agkunkel@gmail.com. 3 WHO Regional Office for Africa, Brazzaville, Republic of the Congo. 4 Global Outbreak Alert and Response Network (GOARN), Geneva, Switzerland. 5 Public Health England, London, UK. 6 UK-Public Health Rapid Support Team, London, UK. 7 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. 8 Sciensano, Brussels, Belgium.  9Ministry of Health of Mauritania, Nouakchott, Mauritania. 10 Provincial Health Division of the Équateur Region, Mbandaka, Democratic Republic of the Congo. 11 WHO Headquarters, Geneva, Switzerland.

 

Abstract

BACKGROUND:

The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system’s implementation.

METHODS:

From 23 June – 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs’ awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff’s awareness of EVD.

RESULTS:

ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses.

CONCLUSION:

HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.

KEYWORDS: Active case finding; Democratic Republic of the Congo; Ebola; Ebola virus disease; Health facility; Surveillance

PMID: 31752717 DOI: 10.1186/s12879-019-4600-4

Keywords: Ebola; DRC.

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An #Evolutionary #Insight into Emerging #Ebolavirus #Strains Isolated in #Africa (J Med Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Med Virol. 2019 Nov 8. doi: 10.1002/jmv.25627. [Epub ahead of print]

An Evolutionary Insight into Emerging Ebolavirus Strains Isolated in Africa.

Pereira-Gomez M1,2, Lopez-Tort F3, Fajardo A1, Cristina J1.

Author information: 1 Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo, 11400, Uruguay. 2 Laboratorio de Inmunovirología, Institut Pasteur de Montevideo, Mataojo 2020, 11400, Montevideo, Uruguay. 3 Laboratorio de Virología Molecular, Sede Salto, Centro Universitario Regional Litoral Norte, Universidad de la República, Gral. Rivera 1350, 50000, Salto, Uruguay.

 

Abstract

BACKGROUND:

On July 19th, 2019, the World Health Organization declared the current Ebola virus (EBOV) outbreak in Congo Democratic Republic (COD) a public health emergency of international concern. To address the potential threat of EBOV evolution outpacing antibody treatment and vaccine efforts, a detailed evolutionary analysis of EBOV strains circulating in different African countries was performed.

METHODS:

Genome composition of EBOV strains were studied using multivariate statistical analysis. To investigate the patterns of evolution of EBOV strains, a Bayesian Markov Chain Monte Carlo (MCMC) approach was used.

RESULTS:

Two different genetic lineages, with a distinct genome composition gave rise to the recent EBOV outbreaks in central and western Africa. Strains isolated in COD in 2018 fall into two different genetic clusters, according to their geographical location of isolation. Different amino acid substitutions among strains from these two clusters have been found, particularly in NP, GP and L proteins. Significant differences in codon and amino acid usage among clusters were found.

CONCLUSION:

Strains isolated in COD in 2018 belongs to two distinct genetic clusters, with distinct codon and amino acid usage. Geographical diversity plays an important role in shaping the molecular evolution of EBOV populations.

This article is protected by copyright. All rights reserved.

KEYWORDS: Ebolavirus; GP protein; codon usage; evolution

PMID: 31702053 DOI: 10.1002/jmv.25627

Keywords: Ebolavirus; Ebola; DRC; Genetics.

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