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Combined Genetic and Chemical Capsid Modifications of Adenovirus-Based Gene Transfer Vectors for Shielding and Targeting
Published on: October 26, 2018
Genetic and antigenic features of the transmitted virus
Brandon F Keele1, Cynthia A Derdeyn
1Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. keelebf@mail.nih.gov
Purpose Of Review:
Methodological and analytical advances in obtaining genetic information during acute HIV infection have provided an unprecedented view into viral transmission and early immune evasion. The findings suggest that a better understanding of the restricted viral diversity that follows mucosal transmission could lead to novel strategies for vaccine, microbicide or other therapeutic interventions.
Recent Findings:
During sexual transmission of HIV-1, viral diversity is reduced presumably due to obstacles an infectious virion must overcome to establish infection within a new host. Recently, single-genome amplification followed by direct sequencing from samples obtained during acute infection has been utilized to quantify the actual number of infecting variants. Overall, the vast majority (over 75%) of new infections were initiated by a single genetic variant. Transmission of multiple variants from a single donor (between two and five) was also observed and is associated with factors that compromise the genital mucosa. These analyses included over 200 patients representing subtypes A, B, C, D and have been reproduced in nonhuman primate model systems.
Summary:
During acute infection, there is limited viral diversity in most patients, which provides a window of opportunity for vaccines or therapies to inhibit or prevent infection. Identifying the common genetic and antigenic properties of newly transmitted viruses will be necessary to advance vaccine design.
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