Echeverría Natalia, Gámbaro Fabiana, Beaucourt Stéphanie, Soñora Martín, Hernández Nelia, Cristina Juan, Moratorio Gonzalo, Moreno Pilar
Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay.
Laboratorio de Evolución Experimental de Virus, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay.
Viruses. 2024 Apr 3;16(4):560. doi: 10.3390/v16040560.
Hepatitis C virus (HCV) remains a significant global health challenge, affecting millions of people worldwide, with chronic infection a persistent threat. Despite the advent of direct-acting antivirals (DAAs), challenges in diagnosis and treatment remain, compounded by the lack of an effective vaccine. The HCV genome, characterized by high genetic variability, consists of eight distinct genotypes and over ninety subtypes, underscoring the complex dynamics of the virus within infected individuals. This study delves into the intriguing realm of HCV genetic diversity, specifically exploring the phenomenon of mixed infections and the subsequent detection of recombinant forms within the conserved internal ribosome entry site (IRES) region. Previous studies have identified recombination as a rare event in HCV. However, our findings challenge this notion by providing the first evidence of 1a/3a (and vice versa) inter-genotypic recombination within the conserved IRES region. Utilizing advanced sequencing methods, such as deep sequencing and molecular cloning, our study reveals mixed infections involving genotypes 1a and 3a. This comprehensive approach not only confirmed the presence of mixed infections, but also identified the existence of recombinant forms not previously seen in the IRES region. The recombinant sequences, although present as low-frequency variants, open new avenues for understanding HCV evolution and adaptation.
丙型肝炎病毒（HCV）仍然是一项重大的全球健康挑战，影响着全球数百万人，慢性感染始终构成威胁。尽管直接作用抗病毒药物（DAAs）已经问世，但诊断和治疗方面的挑战依然存在，而且由于缺乏有效的疫苗，情况更加复杂。HCV基因组具有高度的遗传变异性，由八个不同的基因型和九十多个亚型组成，这凸显了病毒在受感染个体内的复杂动态。本研究深入探讨了HCV遗传多样性这一引人入胜的领域，特别研究了混合感染现象以及随后在保守的内部核糖体进入位点（IRES）区域内检测到的重组形式。先前的研究已将重组确定为HCV中罕见的事件。然而，我们的研究结果对这一观点提出了挑战，首次提供了在保守的IRES区域内1a/3a（反之亦然）基因型间重组的证据。利用深度测序和分子克隆等先进的测序方法，我们的研究揭示了涉及1a和3a基因型的混合感染。这种全面的方法不仅证实了混合感染的存在，还确定了IRES区域以前未见的重组形式的存在。这些重组序列虽然以低频变体的形式存在，却为理解HCV的进化和适应性开辟了新途径。
