Data di Pubblicazione:
2021
Citazione:
A hepatitis B virus causes chronic infections in equids worldwide / A. Rasche, F. Lehmann, N. Goldmann, M. Nagel, A. Moreira-Soto, D. Nobach, I. de Oliveira Carneiro, N. Osterrieder, A.D. Greenwood, E. Steinmann, A.N. Lukashev, G. Schuler, D. Glebe, J.F. Drexler, E.H.C.(. Aguilar-Setien, W. Azab, A. Carluccio, D. Dietrich, C.R. Franke, I. García-Bocanegra, F. García-Lacy, L.M. Jeworoski, J. Jores, R. Kepper, E. Martins Netto, E. Owusu-Dabo, J.R.L. Ribas, C. Roncoroni, P.L. Roppert, A. Rusenov, N. Rusenova, N. Sandev, P.A. Seeber, A. Shnaiderman-Torban, A. Steinman, B. Tegtmeyer, V. Veneziano, M.C. Veronesi, S. Walter, D. Zapryanova. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 1091-6490. - 118:13(2021 Mar), pp. e2013982118.1-e2013982118.9. [10.1073/pnas.2013982118]
Abstract:
Preclinical testing of novel therapeutics for chronic hepatitis B
(CHB) requires suitable animal models. Equids host homologs of
hepatitis C virus (HCV). Because coinfections of hepatitis B virus
(HBV) and HCV occur in humans, we screened 2,917 specimens
from equids from five continents for HBV. We discovered a distinct
HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by
PCR and antibodies against EqHBV in 5.4% of donkeys and zebras.
Molecular, histopathological, and biochemical analyses revealed
that infection patterns of EqHBV resembled those of HBV in humans,
including hepatotropism, moderate liver damage, evolutionary stasis,
and potential horizontal virus transmission. Naturally infected
donkeys showed chronic infections resembling CHB with high viral
loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo
and weak antibody responses. Antibodies against Equid HCV were
codetected in 26.5% of donkeys seropositive for EqHBV, corroborating
susceptibility to both hepatitis viruses. Deltavirus pseudotypes
carrying EqHBV surface proteins were unable to infect
human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting
polypeptide), suggesting alternative viral entry mechanisms.
Both HBV and EqHBV deltavirus pseudotypes infected
primary horse hepatocytes in vitro, supporting a broad host range
for EqHBV among equids and suggesting that horses might be
suitable for EqHBV and HBV infections in vivo. Evolutionary analyses
suggested that EqHBV originated in Africa several thousand
years ago, commensurate with the domestication of donkeys. In
sum, EqHBV naturally infects diverse equids and mimics HBV infection
patterns. Equids provide a unique opportunity for preclinical
testing of novel therapeutics for CHB and to investigate HBV/
HCV interplay upon coinfection.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
HBV; equids; animal model; coinfection; evolution
Elenco autori:
A. Rasche, F. Lehmann, N. Goldmann, M. Nagel, A. Moreira-Soto, D. Nobach, I. de Oliveira Carneiro, N. Osterrieder, A.D. Greenwood, E. Steinmann, A.N. Lukashev, G. Schuler, D. Glebe, J.F. Drexler, E.H.C.(. Aguilar-Setien, W. Azab, A. Carluccio, D. Dietrich, C.R. Franke, I. García-Bocanegra, F. García-Lacy, L.M. Jeworoski, J. Jores, R. Kepper, E. Martins Netto, E. Owusu-Dabo, J.R.L. Ribas, C. Roncoroni, P.L. Roppert, A. Rusenov, N. Rusenova, N. Sandev, P.A. Seeber, A. Shnaiderman-Torban, A. Steinman, B. Tegtmeyer, V. Veneziano, M.C. Veronesi, S. Walter, D. Zapryanova
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