Invitro Study for the Optimal Production of Hepatitis B Virus Subviral Particles for Medical Purposes

Suef, Reda A.; Mohamed, Ezz Elden M.; Mansour, Mohamed; Farag, Mohamed

doi:10.21608/absb.2020.111456

Al-Azhar Bulletin of Science

2020

DOI: 10.21608/absb.2020.111456

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Invitro Study for the Optimal Production of Hepatitis B Virus Subviral Particles for Medical Purposes

Reda A. Suef

Ezz Elden M. Mohamed

Mohamed Mansour

et al.

Abstract: During replication of hepatitis B virus (HBV), HBV infected cells secrete infectious viral particles and large quantities of subviral particles which are assembled from surface protein without a viral genome. For the current study, the cell line of HepG2.2.15 genetically integrated with the HBV surface region was cultured as an expression system for in vitro production of hepatitis B virus subviral particles (HBVsvp) at different time for commercial purposes. Recorded Results showed that culturing and incubati… Show more

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Cited by 2 publications

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Photobiological modulation of hepatoma cell lines and hepatitis B subviral particles secretion in response to 650 nm low level laser treatment

Al-Toukhy,

Suef,

Hassan

et al. 2023

J Egypt Natl Canc Inst

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Background Chronic hepatitis B virus (HBV) infection is a serious global health concern, with an increased incidence and risk of developing cirrhosis and hepatocellular carcinoma (HCC). Patients chronically infected with HBV are likely to experience chronic oxidative stress, leading to mitochondrial dysfunction. Photobiomodulation is induced by the absorption of low-level laser therapy (LLLT) with a red or infrared laser by cytochrome C oxidase enzyme, resulting in mitochondrial photoactivation. Although it is widely used in clinical practice, the use of LLL as adjuvant therapy for persistent HBV infection is uncommon. This study aimed to investigate the effect of LLLT dosage from 2 J/cm2 to 10 J/cm2 of red diode laser (650 nm) on both hepatoma cell lines (HepG2.2.15 [integrated HBV genome stable cell model] and non-integrated HepG2), with a subsequent impact on HBVsvp production. Methods The present study evaluated the effects of different fluences of low-level laser therapy (LLLT) irradiation on various aspects of hepatoma cell behavior, including morphology, viability, ultrastructure, and its impact on HBVsvp synthesis. Results In response to LLLT irradiation, we observed a considerable reduction in viability, proliferation, and HBVsvp production in both hepatoma cell lines HepG2.2.15 and HepG2. Ultrastructural modification of mitochondria and nuclear membranes: This effect was dose, cell type, and time-dependent. Conclusions The use of LLLT may be a promising therapy for HCC and HBV patients by reducing cell proliferation, HBVsvp production, and altering mitochondrial and nuclear structure involved in cellular death inducers. Further research is required to explore its clinical application.

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Photobiological modulation of hepatoma cell lines and hepatitis B subviral particles secretion in response to 650 nm low level laser treatment

Al-Toukhy,

Suef,

Hassan

et al. 2023

J Egypt Natl Canc Inst

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Peripheral NK cell phenotypic alteration and dysfunctional state post hepatitis B subviral particles stimulation in CHB patients: evading immune surveillance

Selim,

Suef,

Saied

et al. 2024

Front. Immunol.

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BackgroundThe relationship between chronic hepatitis B (CHB) infection and natural killer (NK) cell dysfunction is well-established, but the specific role of HBV viral antigens in driving NK cell impairment in patients with CHB remains unclear. This study investigates the modulatory effects of hepatitis B virus subviral particles (HBVsvp, a representative model for HBsAg) on the phenotypic regulation (activating and inhibitory receptors), cytokine production and cytotoxic potential of peripheral blood mononuclear cell-derived natural killer cells (PBMCs-derived NK cell), which contributes to NK cell dysfunction in CHB infection, potentially serving as an effective HBV immune evasion strategy by the virus.MethodsNK cells were isolated from peripheral blood of patients with CHB (n=5) and healthy individuals (n=5), stimulated with HBVsvp. Subsequent flow cytometric characterization involved assessing changes in activating (NKp46 and NKG2D) and inhibitory (CD94) receptors expression, quantifying TNF-α and IFN- γ cytokine secretion, and evaluating the cytotoxic response against HepG2.2.15 cells with subsequent HBVsvp quantification.ResultsIn CHB patients, in vitro exposure of PBMCs-derived NK cell with HBVsvp (represent HBsAg model) significantly reduced NK cell-activating receptors expression (P = 0.022), increased expression of CD94 + NK cells (p = 0.029), accompanied with a reduced TNF-α - IFN-γ cytokine levels, and impaired cytotoxic capacity (evidenced by increased cell proliferation and elevated HBVsvp levels in co-cultures with HepG2.2.15 cells in a time-dependent), relative to healthy donors.ConclusionThese findings suggest that HBVsvp may induce dysfunctional NK cell responses characterized by phenotypic imbalance with subsequent reduction in cytokine and cytotoxic levels, indicating HBVsvp immunosuppressive effect that compromises antiviral defense in CHB patients. These data enhance our understanding of NK cell interactions with HBsAg and highlight the potential for targeting CD94 inhibitory receptors to restore NK cell function as an immunotherapeutic approach. Further clinical research is needed to validate these observations and establish their utility as reliable biomarkers.

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Invitro Study for the Optimal Production of Hepatitis B Virus Subviral Particles for Medical Purposes

Cited by 2 publications

References 32 publications

Photobiological modulation of hepatoma cell lines and hepatitis B subviral particles secretion in response to 650 nm low level laser treatment

Photobiological modulation of hepatoma cell lines and hepatitis B subviral particles secretion in response to 650 nm low level laser treatment

Peripheral NK cell phenotypic alteration and dysfunctional state post hepatitis B subviral particles stimulation in CHB patients: evading immune surveillance

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