scholarly journals HDV-Like Viruses

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1207
Author(s):  
Jimena Pérez-Vargas ◽  
Rémi Pereira de Oliveira ◽  
Stéphanie Jacquet ◽  
Dominique Pontier ◽  
François-Loïc Cosset ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Helper Virus ◽  
Surface Proteins ◽  
Virus Species ◽  
Human Virus ◽  
B Virus ◽  
Novel Virus ◽  
New Evidence ◽  
Delta Virus

Hepatitis delta virus (HDV) is a defective human virus that lacks the ability to produce its own envelope proteins and is thus dependent on the presence of a helper virus, which provides its surface proteins to produce infectious particles. Hepatitis B virus (HBV) was so far thought to be the only helper virus described to be associated with HDV. However, recent studies showed that divergent HDV-like viruses could be detected in fishes, birds, amphibians, and invertebrates, without evidence of any HBV-like agent supporting infection. Another recent study demonstrated that HDV can be transmitted and propagated in experimental infections ex vivo and in vivo by different enveloped viruses unrelated to HBV, including hepatitis C virus (HCV) and flaviviruses such as Dengue and West Nile virus. All this new evidence, in addition to the identification of novel virus species within a large range of hosts in absence of HBV, suggests that deltaviruses may take advantage of a large spectrum of helper viruses and raises questions about HDV origins and evolution.

scholarly journals Expansion, in vivo–ex vivo cycling, and genetic manipulation of primary human hepatocytes

2020 ◽  
Vol 117 (3) ◽  
pp. 1678-1688 ◽  
Author(s):  
Eleftherios Michailidis ◽  
Koen Vercauteren ◽  
Liliana Mancio-Silva ◽  
Linda Andrus ◽  
Cyprien Jahan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Genetic Manipulation ◽  
Ex Vivo ◽  
Pyrrolizidine Alkaloid ◽  
Human Hepatocytes ◽  
Primary Human Hepatocytes ◽  
Short Lifespan ◽  
B Virus ◽  
Donor Variability

Primary human hepatocytes (PHHs) are an essential tool for modeling drug metabolism and liver disease. However, variable plating efficiencies, short lifespan in culture, and resistance to genetic manipulation have limited their use. Here, we show that the pyrrolizidine alkaloid retrorsine improves PHH repopulation of chimeric mice on average 10-fold and rescues the ability of even poorly plateable donor hepatocytes to provide cells for subsequent ex vivo cultures. These mouse-passaged (mp) PHH cultures overcome the marked donor-to-donor variability of cryopreserved PHH and remain functional for months as demonstrated by metabolic assays and infection with hepatitis B virus and Plasmodium falciparum. mpPHH can be efficiently genetically modified in culture, mobilized, and then recultured as spheroids or retransplanted to create highly humanized mice that carry a genetically altered hepatocyte graft. Together, these advances provide flexible tools for the study of human liver disease and evaluation of hepatocyte-targeted gene therapy approaches.

scholarly journals Hepatitis delta virus facilitates the selection of hepatitis B virus mutants in vivo and functionally impacts on their replicative capacity in vitro

2016 ◽  
Vol 22 (1) ◽  
pp. 98.e1-98.e6 ◽  
Author(s):  
E. Shirvani-Dastgerdi ◽  
M.R. Pourkarim ◽  
U. Herbers ◽  
S. Amini-Bavil-Olyaee ◽  
E. Yagmur ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Replicative Capacity ◽  
Hepatitis Delta ◽  
B Virus ◽  
Selection Of ◽  
Delta Virus

scholarly journals Endosomal acidification inhibitors broadly inhibit influenza virus and coronavirus in vivo

2021 ◽  
Author(s):  
Hanjun Zhao ◽  
Hoiyan Lam ◽  
Xinxin Zhou ◽  
Zheng Peng ◽  
Jasper Chan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Ex Vivo ◽  
Endocytic Pathway ◽  
Viral Fusion ◽  
Endosomal Acidification ◽  
B Virus ◽  
Antiviral Activities

Abstract Influenza virus, coronavirus, and drug-resistant viruses are long-term threats to public health because of lacking effective antivirals. Thus, chemicals with broad-spectrum antiviral activities and low possibility to induce drug resistance are urgently needed. Here, we identify a peptidic inhibitor P16 significantly inhibiting influenza A/B virus by binding to HA to block viral fusion. Moreover, P16 antagonizes endosomal acidification to suppress influenza virus and SARS-CoV-2 entry through the endocytic pathway. Importantly, endosomal acidification inhibitor P16 or chloroquine can broadly inhibit A(H1N1) virus, SARS-CoV and SARS-CoV-2 replication in mice and hamsters when administrated through intranasal inoculation or atomization inhalation, contrary to reported treatment failure by systemic route. Chloroquine can significantly inhibit SARS-CoV-2 replication in ex vivo human lung tissues. In conclusion, endosomal acidification inhibitors (P16 and chloroquine) can broadly inhibit influenza virus and coronavirus replication in vivo, which supports atomization inhalation of chloroquine for treating coronavirus and influenza patients in clinical trials.

Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells

Blood ◽  
2005 ◽  
Vol 105 (12) ◽  
pp. 4743-4748 ◽  
Author(s):  
Manuela Battaglia ◽  
Angela Stabilini ◽  
Maria-Grazia Roncarolo
Keyword(s):  
T Cells ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Peripheral Tolerance ◽  
Activation Induced Cell Death ◽  
Naturally Occurring ◽  
New Evidence ◽  
Immunosuppressive Compound

Abstract Rapamycin is an immunosuppressive compound that is currently used to prevent acute graft rejection in humans. In addition, rapamycin has been shown to allow operational tolerance in murine models. However, a direct effect of rapamycin on T regulatory (Tr) cells, which play a key role in induction and maintenance of peripheral tolerance, has not been demonstrated so far. Here, we provide new evidence that rapamycin selectively expands the murine naturally occurring CD4+CD25+FoxP3+ Tr cells in vitro. These expanded Tr cells suppress proliferation of syngeneic T cells in vitro and prevent allograft rejection in vivo. Interestingly, rapamycin does not block activation-induced cell death and proliferation of CD4+ T cells in vitro. Based on this new mode of action, rapamycin can be used to expand CD4+CD25+FoxP3+ Tr cells for ex vivo cellular therapy in T-cell-mediated diseases. (Blood. 2005;105:4743-4748)

scholarly journals Direct demonstration of antigenic substitution of Borrelia burgdorferi ex vivo: exploration of the paradox of the early immune response to outer surface proteins A and C in Lyme disease.

1996 ◽  
Vol 183 (1) ◽  
pp. 261-269 ◽  
Author(s):  
R R Montgomery ◽  
S E Malawista ◽  
K J Feen ◽  
L K Bockenstedt
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Ex Vivo ◽  
Surface Proteins ◽  
Rt Pcr ◽  
Variable Expression ◽  
Outer Surface Proteins ◽  
Direct Demonstration

The outer surface proteins (Osps) of Borrelia burgdorferi, the etiologic agent of Lyme disease, are principle targets of protective immune responses against this organism. Whereas most North American strains of B. burgdorferi in culture express an abundant amount of Osp A, antibodies to this protein are either absent or only weakly detected in the sera of naturally infected patients or experimentally infected mice. In contrast, Osp C, which has variable expression on cultured organisms; elicits an early, strong humoral response. To examine this paradox, we have studied the in vivo adaptation of a cloned population of B. burgdorferi strain N40 during the early course of experimental murine borreliosis. As in human disease, antibodies to Osp A were only weakly present in the early immune repertoire after murine inoculation with low dose (10(3)) spirochetes. In contrast, antibodies to Osp C were prominent, even though on cultured spirochetes Osp C mRNA and protein expression could not be detected by reverse transcription polymerase chain reaction (RT-PCR) or indirect immunofluorescence, respectively. These observations led us to investigate the expression of Osp A and Osp C in vivo. By direct fluorescent staining of uncultured spirochetes ex vivo and by PCR amplification of spirochetal mRNA, we show that Osp C is indeed expressed by some spirochetes after infection in the mouse. Spirochetes expressing Osp A could also be detected within the first 2 wk of infection, but not at 30 d. Osp A mRNA, although present at day 14 of infection, could not be amplified by RT-PCR at day 30, suggesting that the expression of this Osp is transient. This further implies that the late burst in Osp A antibodies in both mice and humans may be anamnestic. These results indicate that either Osp C is upregulated on spirochetes after infection, or Osp C-expressing spirochetes expand preferentially over those expressing Osp A during infection. These results have important implications for vaccine design and offer one explanation for the failure of Osp A antibodies to eradicate spirochetes from the infected host.

scholarly journals A hepatitis B virus causes chronic infections in equids worldwide

2021 ◽  
Vol 118 (13) ◽  
pp. e2013982118
Author(s):  
Andrea Rasche ◽  
Felix Lehmann ◽  
Nora Goldmann ◽  
Michael Nagel ◽  
Andres Moreira-Soto ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Proteins ◽  
Broad Host Range ◽  
Chronic Infections ◽  
Preclinical Testing ◽  
Novel Therapeutics ◽  
B Virus

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.

scholarly journals Unique Properties of the Large Antigen of Hepatitis Delta Virus

1999 ◽  
Vol 73 (9) ◽  
pp. 7147-7152 ◽  
Author(s):  
Gloria Moraleda ◽  
Steven Seeholzer ◽  
Vadim Bichko ◽  
Roland Dunbrack ◽  
James Otto ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Surface Proteins ◽  
Translation System ◽  
Dimerization Domain ◽  
Particle Assembly ◽  
Hepatitis Delta ◽  
C Terminus ◽  
Delta Virus

ABSTRACT The large form of the hepatitis delta virus (HDV) protein (L) can be isoprenylated near its C terminus, and this modification is considered essential for particle assembly. Using gel electrophoresis, we separated L into two species of similar mobilities. The slower species could be labeled by the incorporation of [14C]mevalonolactone and is interpreted to be isoprenylated L (Li). In serum particles, infected liver, transfected cells, and assembled particles, 25 to 85% of L was isoprenylated. Isoprenylation was also demonstrated by 14C incorporation in vitro with a rabbit reticulocyte coupled transcription-translation system. However, the species obtained migrated even slower than that detected by labeling in vivo. Next, in studies of HDV particle assembly in the presence of the surface proteins of human hepatitis B virus, we observed the following. (i) Relative to L, Li was preferentially assembled into virus-like particles. (ii) Li could coassemble the unmodified L and the small delta protein, S. (iii) In contrast, a form of L with a deletion in the dimerization domain was both isoprenylated and assembled, but it could not support the coassembly of S. Finally, to test the expectation that the isoprenylation of L would increase its hydrophobicity, we applied a phase separation strategy based on micelle formation with the nonionic detergent Triton X-114. We showed the following. (i) The unique C-terminal 19 amino acids present on L relative to S caused a significant increase in the hydrophobicity. (ii) This increase was independent of isoprenylation. (iii) In contrast, other, artificial modifications at either the N or C terminus of S did not increase the hydrophobicity. (iv) The increased hydrophobicity was not sufficient for particle assembly; nevertheless, we speculate that it might facilitate virion assembly.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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