Molecular analysis and ex vivo infectivity of seronegative occult hepatitis C virus: a study in single haemodialysis centre

Abdul Rahman, Siti Nurul Fazlin and Hamzah, Hairul Aini and Mahmud, Mohammed Imad A. Mustafa and Mat Harun, Noraihan (2024) Molecular analysis and ex vivo infectivity of seronegative occult hepatitis C virus: a study in single haemodialysis centre. Malaysian Journal of Medical Sciences, 31 (2). pp. 30-42. ISSN 1394-195X E-ISSN 2180-4303

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Abstract

Background: In occult hepatitis C virus infection (OCI), hepatitis C virus ribonucleic acid (HCV RNA) is detectable in peripheral blood mononuclear cells (PBMCs) but is not evident in serum or plasma. Understanding of OCI in patients with seronegative anti-HCV antibodies is limited. Methods: In this study, six HCV isolates from haemodialysis (HD) patients with seronegative OCI were identified by molecular assays and phylogenetic analysis. The virus infectivity was assessed ex vivo using a primary naïve PBMC culture system. HCV isolates obtained from the PBMCs of 10 patients with chronic HCV infection (CCI) were characterised concurrently and used as positive controls in the cell culture. Results: Sequence analysis of the 5ʹ untranslated region (UTR) and non-structural 5B (NS5B) region revealed that HCV genotype 3 was the most prevalent virus type in both the OCI and CCI groups. One of the occult HCV isolates was identified as a mixed type. The mean viral load (log10 RNA copies/106 cells) in the PBMC samples of the OCI group (M = 3.4, SD = 0.7) was lower than that of the CCI group (M = 4.6, SD = 1.7). Upon culture, de novo OCI-HCV replicates were detected in five out of six naïve PBMC cultures. Analysis of the replicates showed a single guanine addition in the domain III of 5’-UTR but the overall molecular structure was retained. Conclusion: Seronegative OCI is an active form of infection that replicates at a low level in PBMCs. Seronegative OCI may share the same route of transmission as CCI. The retained viral competency may have an implication for its persistence.

Item Type:	Article (Journal)
Uncontrolled Keywords:	hepatitis C virus, patients, PBMCs, sequence analysis, genotype
Subjects:	Q Science > QR Microbiology Q Science > QR Microbiology > QR355 Virology R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Basic Medical Kulliyyah of Medicine
Depositing User:	Dr Hairul Aini Hamzah
Date Deposited:	02 May 2024 10:58
Last Modified:	02 May 2024 10:58
URI:	http://irep.iium.edu.my/id/eprint/112008

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