Whole-Genome Sequence Analysis of Human Papillomavirus Type 18 from Infected Thai Women

Abstract

Objective: The aim of this study was to attain molecular knowledge of human papillomavirus type 18 (HPV18) by sequencing the whole genome of HPV18 isolated from Thai women at various clinical stages of disease progression. Method: Our group analyzed 9 samples of whole-genome HPV18 in infected women ranging from normal to cervical cancer by PCR, a sequencing method and bioinformatics programs. Results: Phylogenetic analysis based on the whole genome showed that HPV18 samples were more closely related to the European and Asian-American type than the African type. The vaccine strain’s L1 nucleotide (US patent 5820870) showed a close relationship to the African type. However, our data cannot indicate the correlation between cytological data and nucleotide or amino acid variation. Conclusion: Our group cannot draw any inference between the clinical stage of disease progression and amino acid alterations as there were only 1 or 2 samples available for each clinical trial. However, we hope that these new data on the HPV genome, which are representative of the entire genome of HPV in Southeast Asia, can serve as basis data for future research on the pathogenesis of cervical cancer. Additionally, the second-generation HPV18 vaccines should be tested on both HPV18-L1 and HPV18-L2 for increasing potential protection.

Human Papillomavirus 18 Genetic Variation and Cervical Cancer Risk Worldwide

“…We additionally showed that C lineage variants were highly specific for Africa, although they were rarely detected in our series and appear to have been present in only a few cases in previous studies (12,13,46,47). Of note, the A5 sublineage, which has only recently been reported in a single isolate from Thailand (13,54), was found in a higher proportion of samples from northern Africa than elsewhere. The fact that the LCR of A5 sublineage variants share many features with B and C lineage variants suggests that northern African HPV18 isolates represent a previously understudied branch of HPV18 evolution, as observed for HPV16 (51).…”

Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2

“…18 A cross-neutralizing monoclonal anti-L2 antibody, K4L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , highly potent at neutralizing HPV 16 and other high-risk HPV pseudovirions (PSV), fails to neutralize HPV 31. Vice versa, an anti-HPV 31 L2 neutralizing antibody (K3L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] ) is not able to neutralize HPV 16 PSV. Also, anti-HPV 16 L2 polyclonal sera neutralize HPV 31 pseudovirions with a low efficiency (Seitz et al, unpublished data).…”

“…Of the 24 HPV 18 L2 sequences, two sequences (8%) possessed a P33H 29 exchange, one sequence (4%) contained a P33N 30 exchange and four sequences (17%) yielded a double exchange P29S þ P33N 29 (Fig. 2).…”

“…Two monoclonal antibodies, K18L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and K3L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , as well as five polyclonal sera were tested on the HPV 31 reference and variant pseudovirions in a neutralization assay. Although K18L2 [20][21][22][23][24][25][26][27][28][29][30][31][32]…”

“…Neutralization of HPV 18 P33H, P33N and P29S 1 P33N L2 variants HPV 18 L2 reference, P33H, P33N and P29S þ P33N pseudovirions were tested in an in vitro neutralization assay with cross-neutralizing antibodies K4L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and K18L2 20-38 and 10 polyclonal sera.…”