The use of peptides for deciphering the mechanism of EBV, HPV, and HCV invasion of human cells

Epstein-Barr virus (EBV), human papillomavirus (HPV), and hepatitis C virus (HCV) are significant human pathogens associated with various diseases, employing complex molecular mechanisms for cellular entry and immune evasion. Peptide-based research, using more than 700 synthetic peptides, has deciphered some of the molecular interactions between viral proteins and host cell receptors, offering promising diagnostics and therapeutic strategies. In EBV, binding peptides have been identified: 11382, 11389, and 11416 derived from gp350/220; 11435, 11436, and 11438 from gp85 [glycoprotein H (gH)]; and 11521 from BNRF1/p140. Most of these peptide sequences are surface-exposed and are part of the contact regions with human cell receptors, making them promising candidates for strategies aimed at inhibiting EBV invasion of human cells. Peptide 11382 is the target of the neutralizing antibody 72A1; peptides 11382 and 11416 induce interleukin-6 production; peptide 11435 binds to integrin αvβ6, and peptide 11438 triggers a cytokine storm. In the HPV L1 protein, a major component of the viral capsid, peptides 18283 and 18294 have been identified as epithelial cell-binding peptides located on the virus surface. Parts of the sequences are recognized by anti-HPV neutralizing antibodies. These two peptides, along with peptide 18301, have been identified as potential biomarkers for HPV infection because they are recognized by antibodies elicited during natural HPV infection, making them suitable targets for serological detection. In the envelope proteins E1 and E2 from HCV, five hepatocyte- and CD81-positive cell-binding peptides have been identified. The sequences of these peptides contain linear B-cell epitopes recognized by neutralizing antibodies, and some of them have been used to develop serological tests for determining HCV infection. Peptide-based approaches can lead to innovative strategies for the prevention, diagnosis, and treatment of these viral diseases. Additionally, these peptides and their sequences can be used to modulate the immune response and generate tools for cancer theragnostic.