Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity.

Yuanyuan Hu,Kunxue Hong,Li Ren,Yuhua Ruan,Zheng Wang,Xintao Hu,Shasha Sun,Sen Zou,Yiming Shao,Ying Liu,Yanling Hao,Liying Ma

doi:10.3390/vaccines9040311

Abstract

We sought to analyze the evolutionary characteristics and neutralization sensitivity of viruses in a human immunodeficiency virus type 1 (HIV-1) subtype B′ infected plasma donor with broadly neutralizing activity, which may provide information for new broadly neutralizing antibodies (bNAbs) isolation and immunogen design. A total of 83 full-length envelope genes were obtained by single-genome amplification (SGA) from the patient’s plasma at three consecutive time points (2005, 2006, and 2008) spanning four years. In addition, 28 Env-pseudotyped viruses were constructed and their neutralization sensitivity to autologous plasma and several representative bNAbs were measured. Phylogenetic analysis showed that these env sequences formed two evolutionary clusters (Cluster I and II). Cluster I viruses vanished in 2006 and then appeared as recombinants two years later. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs, including 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. We confirmed that HIV-1 continued to evolve even in the presence of bNAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.

Highlights

Despite nearly 40 years of effort, human immunodeficiency virus type 1 (HIV-1) infection is still a major health threat around the globe
We investigated the characteristics of sequential HIV-1 envelope sequences and virus neutralization sensitivity to autologous plasmas and several well-known broadly neutralizing antibodies (bNAbs) in a plasma donor CBJC515 with broadly neutralizing activity, to identify features that potentially contribute to the immunogenic properties of the envelope proteins
A total of 83 full-length HIV-1 env gene sequences longitudinally from three time points spanning four years formed two evolutionary clusters (Cluster I and II), which evolved in different ways

Summary

Introduction

Despite nearly 40 years of effort, human immunodeficiency virus type 1 (HIV-1) infection is still a major health threat around the globe. It can create a new combination of existing genetic polymorphisms in a single replication cycle, allowing the virus to acquire a broader phenotype and have more opportunities to escape immune stress [3]. BNAbs can protect against Simian/Human Immunodefiency Virus (SHIV) challenge in animal experiments [9,10] and control virus rebound in clinical trials [11,12]. They provide the promise of helping to guide vaccine and therapeutic strategy development

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Conclusion