The propagation of HSV-1 in high autophagic activity

Microb Pathog. 2021 Mar:152:104599. doi: 10.1016/j.micpath.2020.104599. Epub 2020 Nov 2.


Autophagy is an intracellular process involving double-membrane vacuoles that ultimately merge with the lysosomes and play a key role in the inhibition of herpessimplex virus 1 (HSV-1) proliferation. This virus is an agent of some lethal neuronal diseases like encephalitis. HSV-1 requires the expression of its latent proteins, such as ICP34.5, to promote cell infection, which disrupts the autophagy process. In this study, we aimed to evaluate the effect of autophagy induction on HSV-1 replication in host cells at the early and late stages of its replication. Furthermore, we explored the consequences of autophagy induction before and after cell infection.Cells were transfected through Beclin-1-expressing plasmids. Autophagy induction was performed with microtubule-associated protein 1 light chain 3 (LC3-II) as an autophagosome formation marker by using flow cytometry. In the first stage, HSV-1 was inoculated into transfected cells 18 hours post-transfection. Next, viral DNA was extracted 18 and 48 hours post-infection, and eventually viral copies per milliliter were calculated through real-time polymerase chain reaction (PCR). For the second stage, the plasmid containing Beclin-1 was transfected to the cells following virus inoculation to examine the influence of autophagy induction after cell infection.Study results have shown that in neuroblastoma cells autophagy activation reduces virus yield from 4×10 5 copies/ml (control sample) to 9×10 4 copies/ml at 24 h postinfection and viral load after 48 h declines up to 1×10 6 copies/ml, which is less than that of the control sample about 5 logs. However, in HeLa cells, we observed a significant reduction in autophagy induction with reducing HSV-1 propagation. Despite these results, HSV-1 proliferation in both cell types increased and these viruses were able to maintain their ability to propagate even in high autophagic activity. Hyperactivation of autophagy can only slow the rate of virus replication. This study may provide new insight into the effect of autophagy on HSV-1 replication.

Keywords: Autophagy; Beclin-1; HeLa cell; Neuroblastoma cell.

MeSH terms

  • Autophagy
  • HeLa Cells
  • Herpesvirus 1, Human*
  • Humans
  • Vacuoles
  • Virus Replication