Genetic variability in minor capsid protein (L2 gene) of human papillomavirus type 16 among Indian women

Human papillomavirus type 16 (HPV-16) is the predominant genotype worldwide associated with invasive cervical cancer and hence remains as the focus for diagnostic development and vaccine research. L2, the minor capsid protein forms the packaging unit for the HPV genome along with the L1 protein and is primarily associated with transport of genomic DNA to the nucleus. Unlike L1, L2 is known to elicit cross-neutralizing antibodies and thus becomes a suitable candidate for pan-HPV prophylactic vaccine development. In the present study, a total of 148 cervical HPV-16 isolates from Indian women were analyzed by PCR-directed sequencing, phylogenetic analysis and in silico immunoinformatics tools to determine the L2 variations that may impact the immune response and oncogenesis. Ninety-one SNPs translating to 35 non-synonymous amino acid substitutions were observed, of these 16 substitutions are reported in the Indian isolates for the first time. T245A, L266F, S378V and S384A substitutions were significantly associated with high-grade cervical neoplastic status. Multiple substitutions were observed in samples from high-grade cervical neoplastic status as compared to those from normal cervical status (p = 0.027), specifically from the D3 sub-lineage. It was observed that substitution T85A was part of both, B and T cell epitopes recognized by MHC-I molecules; T245A was common to B and T cell epitopes recognized by MHC-II molecules and S122P/A was common to the region recognized by both MHC-I and MHC-II molecules. These findings reporting L2 protein substitutions have implications on cervical oncogenesis and design of next-generation L2-based HPV vaccines.