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Article: Evaluation and Immunogenicity of Combined Liposome-Based Vaccine Candidates against Hepatitis E and B Viruses in Rhesus Monkeys.

Deshmukh, Tejaswini / Shah, Rachita / Devhare, Pradip / Lole, Kavita / Arankalle, Vidya

2024 Volume 12, Issue 1

Abstract: The administration of vaccines using a combination approach ensures better coverage and reduces the number of injections and cost. The present study assessed liposome-complexed DNA-corresponding proteins of hepatitis E and B viruses (HEV and HBV) as ... ...

Abstract	The administration of vaccines using a combination approach ensures better coverage and reduces the number of injections and cost. The present study assessed liposome-complexed DNA-corresponding proteins of hepatitis E and B viruses (HEV and HBV) as combined vaccine candidates in rhesus monkeys. The HEV and HBV components consisted of 450 bps, neutralizing the epitope/s (NE) region, and 685 bps small (S) envelope gene-corresponding proteins, respectively. Three groups (
Language	English
Publishing date	2024-01-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines12010053
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Article ; Online: Repurposing of artesunate, an antimalarial drug, as a potential inhibitor of hepatitis E virus.

Bhise, Neha / Agarwal, Megha / Thakur, Nidhi / Akshay, P S / Cherian, Sarah / Lole, Kavita

Archives of virology

2023 Volume 168, Issue 5, Page(s) 147

Abstract: Hepatitis E virus (HEV) is endemic in several developing countries of Africa and Asia. It mainly causes self-limiting waterborne infections, in either sporadic or outbreak form. Recently, HEV was shown to cause chronic infections in immunosuppressed ... ...

Abstract	Hepatitis E virus (HEV) is endemic in several developing countries of Africa and Asia. It mainly causes self-limiting waterborne infections, in either sporadic or outbreak form. Recently, HEV was shown to cause chronic infections in immunosuppressed individuals. Ribavirin and interferon, the current off-label treatment options for hepatitis E, have several side effects. Hence, there is a need for new drugs. We evaluated the antimalarial drug artesunate (ART) against genotype 1 HEV (HEV-1) and HEV-3 using a virus-replicon-based cell culture system. ART exhibited 59% and 43% inhibition of HEV-1 and HEV-3, respectively, at the highest nontoxic concentration. Computational molecular docking analysis showed that ART can bind to the helicase active site (affinity score, -7.4 kcal/mol), indicating its potential to affect ATP hydrolysis activity. An in vitro ATPase activity assay of the helicase indeed showed 24% and 55% inhibition at 19.5 µM (EC
MeSH term(s)	Female ; Pregnancy ; Animals ; Humans ; Hepatitis E virus/genetics ; Artesunate/pharmacology ; Artesunate/therapeutic use ; Antimalarials/pharmacology ; Drug Repositioning ; Molecular Docking Simulation ; Virus Replication ; Hepatitis E/drug therapy ; RNA-Dependent RNA Polymerase/genetics ; Adenosine Triphosphate
Chemical Substances	Artesunate (60W3249T9M) ; Antimalarials ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-04-28
Publishing country	Austria
Document type	Journal Article
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-023-05770-1
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Article ; Online: Correction to: Repurposing of artesunate, an antimalarial drug, as a potential inhibitor of hepatitis E virus.

Bhise, Neha / Agarwal, Megha / Thakur, Nidhi / Akshay, P S / Cherian, Sarah / Lole, Kavita

Archives of virology

2023 Volume 168, Issue 7, Page(s) 193

Language	English
Publishing date	2023-06-28
Publishing country	Austria
Document type	Published Erratum
ZDB-ID	7491-3
ISSN	1432-8798 ; 0304-8608
ISSN (online)	1432-8798
ISSN	0304-8608
DOI	10.1007/s00705-023-05799-2
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Article ; Online: Modulation of cellular autophagy by genotype 1 hepatitis E virus ORF3 protein.

Srivastava, Manjita / Bhukya, Prudhvi Lal / Barman, Muneesh Kumar / Bhise, Neha / Lole, Kavita S

The Journal of general virology

2023 Volume 104, Issue 2

Abstract: Hepatitis E virus (HEV) egresses from infected hepatocytes as quasienveloped particles containing open reading frame 3 (ORF3) protein. HEV ORF3 (small phosphoprotein) interacts with host proteins to establish a favourable environment for virus ... ...

Abstract	Hepatitis E virus (HEV) egresses from infected hepatocytes as quasienveloped particles containing open reading frame 3 (ORF3) protein. HEV ORF3 (small phosphoprotein) interacts with host proteins to establish a favourable environment for virus replication. It is a functional viroporin that plays an important role during virus release. Our study provides evidence that pORF3 plays a pivotal role in inducing Beclin1-mediated autophagy that helps HEV-1 replication as well as its exit from cells. The ORF3 interacts with host proteins involved in regulation of transcriptional activity, immune response, cellular and molecular processes, and modulation of autophagy, by interacting with proteins, DAPK1, ATG2B, ATG16L2 and also several histone deacetylases (HDACs). For autophagy induction, the ORF3 utilizes non-canonical NF-κB2 pathway and sequesters p52NF-κB and HDAC2 to upregulate DAPK1 expression, leading to enhanced Beclin1 phosphorylation. By sequestering several HDACs, HEV may prevent histone deacetylation to maintain overall cellular transcription intact to promote cell survival. Our findings highlight a novel crosstalk between cell survival pathways participating in ORF3-mediated autophagy.
MeSH term(s)	Humans ; Autophagy ; Autophagy-Related Proteins/metabolism ; Beclin-1/genetics ; Beclin-1/metabolism ; Genotype ; Hepatitis E ; Hepatitis E virus/genetics ; Hepatocytes ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
Chemical Substances	ATG2B protein, human ; Autophagy-Related Proteins ; Beclin-1 ; Vesicular Transport Proteins ; ORF3 protein, Hepatitis E virus
Language	English
Publishing date	2023-02-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001824
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Article ; Online: Transcriptome analysis of hepatoma cells transfected with Basal Core Promoter (BCP) and Pre-Core (PC) mutant hepatitis B virus full genome construct.

Bhukya, Prudhvi Lal / C, Vignesh Kumar / Lole, Kavita S

The Journal of general virology

2021 Volume 102, Issue 3

Abstract: Infections with Basal Core Promoter (BCP) (A1762T/G1764A) and Pre-Core (PC) (G1896A) hepatitis B virus HBeAg mutants are associated with severe liver injury. We analysed host cell responses in HepG2/C3A, hepatoma cells transfected with infectious clones ... ...

Abstract	Infections with Basal Core Promoter (BCP) (A1762T/G1764A) and Pre-Core (PC) (G1896A) hepatitis B virus HBeAg mutants are associated with severe liver injury. We analysed host cell responses in HepG2/C3A, hepatoma cells transfected with infectious clones developed from genotype D wild type (WT) and BCP/PC mutant (MT) viruses isolated from an acute resolved and an acute liver failure hepatitis B case respectively. Cells transfected with MT virus construct showed ~55 % apoptosis and with WT ~30 % apoptosis at 72 h. To determine possible roles of HBe and HBx proteins in apoptosis, we cloned these genes and co-transfected cells with WT+HBe/HBx or MT+HBe/HBx constructs. Co-expression of HBe protein improved cell viability significantly in both WT and MT virus constructs, indicating an important role of HBe in protecting cells. RNA sequencing analysis carried out at 12 and 72 h post-transfection with WT virus construct showed enrichment of innate/adaptive immune response-activating signal transduction, cell survival and amino acid/nucleic acid biosynthetic pathways at 12 and 72 h. By contrast, MT virus construct showed enrichment in host defence pathways and some biosynthetic pathways at the early time point (12 h), and inflammatory response, secretary granule, regulation of membrane potential and stress response regulatory pathways at the late time point (72 h). There was a significant down-regulation of genes involved in endoplasmic reticulum and mitochondrial functions and metabolism with MT construct and this possibly led to induction of apoptosis in cells. Considering rapid apoptotic changes in cells transfected with MT construct, it can be speculated that HBeAg plays a crucial role in cell survival. It enhances induction of metabolic and synthetic pathways and facilitates management of cellular stress that is induced due to hepatitis B virus infection/replication.
MeSH term(s)	Apoptosis ; DNA, Viral/genetics ; Gene Expression Profiling ; Genotype ; Hepatitis B Core Antigens/genetics ; Hepatitis B e Antigens/genetics ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/pathology ; Hepatitis B, Chronic/virology ; Humans ; Mutation ; Promoter Regions, Genetic ; Transfection ; Viral Core Proteins/genetics
Chemical Substances	DNA, Viral ; Hepatitis B Core Antigens ; Hepatitis B e Antigens ; Viral Core Proteins
Language	English
Publishing date	2021-02-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001568
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Article ; Online: Declining trends in Hepatitis A seroprevalence over the past two decades, 1998-2017, in Pune, Western India.

Deoshatwar, Avinash R / Gurav, Yogesh K / Lole, Kavita S

Epidemiology and infection

2020 Volume 148, Page(s) e121

Abstract: Reduction in seroprevalence of Hepatitis A virus (HAV) is known to be associated with improvements in socioeconomic conditions of the community. National Institute of Virology, Pune has been studying seroprevalence of hepatitis viruses in Pune region ... ...

Abstract	Reduction in seroprevalence of Hepatitis A virus (HAV) is known to be associated with improvements in socioeconomic conditions of the community. National Institute of Virology, Pune has been studying seroprevalence of hepatitis viruses in Pune region over the past four decades. In total, 1438 samples were collected from urban general (UGEN), urban lower socioeconomic stratum (ULSES) and rural (RURAL) populations of the Pune district. Based on estimates in previous studies, subjects were enrolled from age groups '6-10', '15-25' and '40 + ' years. HAV seroprevalence in younger population showed a significant decline. A significant decline in HAV seroprevalence in '15-25' years age group in UGEN (from 85.9% to 73.9%; OR = 0.46, 95% CI: 0.25-0.86) and RURAL (from 98.6% to 91.4%; OR = 0.15, 95% CI: 0.05-0.45) populations suggested that the trend probably started more than a decade ago. Seroprevalence of HAV among ULSES '6-10' children was found to be significantly higher (70.4%) than that among the RURAL children (44.2%; OR = 3.0, 95%CI: 1.7-5.2) and UGEN children (40.4%; OR = 3.5, 95%CI: 1.8-6.7). In view of increasing rates of urbanisation in India, ULSES population needs special consideration while designing future studies and viral hepatitis vaccination/elimination strategies. Our findings call for robust population-based studies that consider heterogeneity within populations and dynamics of socio-economic parameters in various regions of a country.
MeSH term(s)	Adolescent ; Adult ; Child ; Hepatitis A/epidemiology ; Humans ; India/epidemiology ; Population Surveillance ; Retrospective Studies ; Risk Factors ; Seroepidemiologic Studies ; Young Adult
Language	English
Publishing date	2020-05-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632982-2
ISSN	1469-4409 ; 0950-2688
ISSN (online)	1469-4409
ISSN	0950-2688
DOI	10.1017/S0950268820000953
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Article: Editorial: Translational research in hepatitis E, Vol II.

Kramvis, Anna / Pérez-Gracia, Maria Teresa / Lole, Kavita Satish / Rodriguez-Iglesias, Manuel / Shalimar, None

Frontiers in microbiology

2022 Volume 13, Page(s) 1011779

Language	English
Publishing date	2022-08-24
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2022.1011779
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Article ; Online: Metagenomic Analysis of Viromes of

Gangopadhayya, Abhranil / Lole, Kavita / Ghuge, Onkar / Ramdasi, Ashwini / Kamble, Asmita / Roy, Diya / Thakar, Shivani / Nath, Amol / Sudeep, A B / Cherian, Sarah

Viruses

2024 Volume 16, Issue 1

Abstract: Metagenomic analysis ... ...

Abstract	Metagenomic analysis of
MeSH term(s)	Animals ; Swine ; Humans ; Aedes ; African Swine Fever Virus ; Virome ; India ; Bacteriophages ; Arenaviridae ; Granulovirus
Language	English
Publishing date	2024-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010109
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Article ; Online: Application of a truncated ORF2 protein-based ELISA for diagnosis of hepatitis E in an endemic area

Deshmukh, Tejaswini Mahesh / Dudhmal, Manisha Tukaram / Thorat, Neeta Changdeo / Sarje, Prakash Dnyaneshwar / Walimbe, Atul M. / Lole, Kavita Satish

Appl Microbiol Biotechnol. 2022 Dec., v. 106, no. 24 p.8259-8272

2022

Abstract: Enterically transmitted waterborne hepatitis E (HE) caused due to hepatitis E virus (HEV) prevails as a significant public health problem endemic to India. Due to short-term viremia/fecal excretion and poor in vitro transmissibility of HEV, HE diagnosis ... ...

Abstract	Enterically transmitted waterborne hepatitis E (HE) caused due to hepatitis E virus (HEV) prevails as a significant public health problem endemic to India. Due to short-term viremia/fecal excretion and poor in vitro transmissibility of HEV, HE diagnosis depends on detection of specific IgM antibodies in serum. Present study evaluated performances of two in-house and six commercial IgM detection enzyme-linked immunosorbent assays (ELISAs) using sera collected from volunteers/acute hepatitis patients (n = 716). The in-house ELISAs were based on complete and truncated open reading frame 2 (ORF2) proteins containing neutralizing epitope/s region of genotype 1 HEV (ORF2p, 1–660 amino acid (a.a.) and T1NEp, 458–607 a.a., respectively). The commercial ELISAs included Wantai (China), MP Diagnostics (MPD) (Singapore), DIA.PRO Diagnostics (Italy), MBS (Italy), abia (Germany), and ImmunoVision (USA). T1NE ELISA showed 97.0% positive percent agreement (PPA), 99.4% negative percent agreement (NPA), and 98.6% concordance (κ = 0.97, P = 0.0000) with ORF2 ELISA. ORF2, T1NE, Wantai, and MPD ELISAs agreed on results for 88% of sera tested. Two percent sera showed reactivity in each combination of three and two of aforementioned four ELISAs. Remaining 8% sera were single ELISA reactive. PPA and NPA value ranges were 76.3–99.0% and 84.8–99.5%, respectively. Pairwise concordances between all the eight ELISAs ranged from 88.0 to 100% (κ: 0.74–1.00). Both the in-house ELISAs agreed better with Wantai over MPD ELISA. In conclusion, both ORF2 and T1NE ELISAs were equally efficient in diagnosing HEV infections. T1NEp proved to be an excellent tool in HE sero-diagnosis and is worth exploring in development of simple rapid tests. KEY POINTS: • In-house ELISA based on bacterially expressed neutralizing epitope/s region protein • In-house ELISA based on complete ORF2 protein expressed in insect cells • Comparison of two in-house and six commercial anti-HEV IgM antibody detection ELISAs
Keywords	Orthohepevirus A ; Singapore ; amino acids ; antibody detection ; blood serum ; diagnostic techniques ; epitopes ; excretion ; genotype ; hepatitis E ; insects ; public health ; serodiagnosis ; viremia ; China ; Germany ; India ; Italy
Language	English
Dates of publication	2022-12
Size	p. 8259-8272.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	392453-1
ISSN	1432-0614 ; 0171-1741 ; 0175-7598
ISSN (online)	1432-0614
ISSN	0171-1741 ; 0175-7598
DOI	10.1007/s00253-022-12271-9
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Article ; Online: Hepatitis E virus ORF1 encoded non structural protein-host protein interaction network.

Ojha, Nishant Kumar / Lole, Kavita S

Virus research

2016 Volume 213, Page(s) 195–204

Abstract: Hepatitis E virus ORF1 encoded non-structural polyprotein (nsP) consist of multiple domains, namely: Methyltransferase, Y-domain, Protease, X-domain, Helicase and RNA dependent RNA polymerase. We have attempted to identify human liver cell proteins that ... ...

Abstract	Hepatitis E virus ORF1 encoded non-structural polyprotein (nsP) consist of multiple domains, namely: Methyltransferase, Y-domain, Protease, X-domain, Helicase and RNA dependent RNA polymerase. We have attempted to identify human liver cell proteins that are interacting with HEV ORF1 encoded functional domains by using Y2H screening. A total of 155 protein-protein interactions between HEV-ORF1 and human proteins were identified. Comparative analysis of the HEV-ORF1-Human interaction network with reconstructed human interactome showed that the cellular proteins interacting with HEV-ORF1 are central and interconnected. Enrichment analysis of Gene Ontology and cellular pathways showed that the viral proteins preferentially interacted with the proteins of metabolism and energy generation along with host immune response and ubiquitin proteasomal pathways. The mTOR and focal adhesion pathways were also targeted by the virus. These interactions suggest that HEV probably utilizes important proteins in carbohydrate metabolism, energy generation and iron homoeostasis in the host cells during its establishment.
MeSH term(s)	Hepatitis E virus/physiology ; Hepatocytes/chemistry ; Hepatocytes/virology ; Host-Pathogen Interactions ; Humans ; Protein Interaction Maps ; Two-Hybrid System Techniques ; Viral Nonstructural Proteins/metabolism
Chemical Substances	Viral Nonstructural Proteins
Language	English
Publishing date	2016-02-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2015.12.007
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