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      The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics

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          Abstract

          Human papillomavirus 52 (HPV52) infection is prevalent in the Chinese population, and variations in HPV52 show correlations with oncogenicity. However, no specific variation in HPV52 was reported to show relevancy to infection characteristics. In this study, we retrieved 222 isolates of E6 and L1 full-length genes from 197 Chinese women with HPV52 infection. After sequence alignment and phylogenetic tree construction, we found that 98.39 % of the collected variants belonged to the sublineage B2 and two variants displayed incongruence between the phylogenetic tree of E6 and L1. The analysis of the infection pattern showed that the presence of C6480A/T mutation in the L1 gene was associated with single infection ( P=0.01) and persistent infection ( P=0.047) of HPV52, while the A6516G nucleotide change was relevant to transient infection ( P=0.018). Our data also indicated that variations T309C in the E6 gene and C6480T, C6600A in L1 were more commonly presented in patients with high-grade cytology ( P<0.05). One HPV52 breakthrough infection after vaccination was identified, which hinted at the immune escape post-vaccination. Young coitarche age and non-condom usage were correlated to multiple infections. This study provided insight into the polymorphism of HPV52 and revealed the impact of variations in HPV52 on its infection characteristics.

          Most cited references42

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          MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.

          The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.
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            Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

            Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.
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              Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera

              The race to produce vaccines against SARS-CoV-2 began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK–B.1.1.7, South Africa–B.1.351 and Brazil–P.1. These variants have multiple changes in the immunodominant spike protein which facilitates viral cell entry via the Angiotensin converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.

                Author and article information

                Journal
                Microb Genom
                Microb Genom
                mgen
                mgen
                Microbial Genomics
                Microbiology Society
                2057-5858
                2023
                27 April 2023
                27 April 2023
                : 9
                : 4
                : mgen000962
                Affiliations
                [ 1] departmentDepartment of Gynecology and Obstetrics , Obstetrics and Gynecology Hospital of Fudan University , Shanghai, PR China
                [ 2] departmentDepartment of Obstetrics and Gynecology , Shanghai Changning Maternity and Infant Health Hospital , Shanghai, PR China
                [ 3] departmentDepartment of Obstetrics and Gynecology , Shanghai Pudong Hospital of Fudan University , Shanghai, PR China
                Author notes
                [†]

                These authors contributed equally to this work

                *Correspondence: Yanyun Li, liyanyun@ 123456fudan.edu.cn
                *Correspondence: Long Sui, suilong@ 123456fudan.edu.cn
                Article
                000962
                10.1099/mgen.0.000962
                10210937
                37103992
                a8bfc337-f5bb-486d-a113-82c515dc8352
                © 2023 The Authors

                This is an open-access article distributed under the terms of the Creative Commons Attribution License.

                History
                : 17 August 2022
                : 15 January 2023
                Funding
                Funded by: Science and Technology Commission of Shanghai Municipality
                Award ID: 21Y11906500
                Award Recipient : LiYanyun
                Funded by: National Natural Science Foundation of China
                Award ID: 82272970
                Award Recipient : LiYanyun
                Categories
                Research Articles
                Pathogens and Epidemiology
                Custom metadata
                0

                human papillomavirus,variation,persistent infection,multiple infection,vaccine breakthrough infection,cervical cancer

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