Year-end Sale % OFF 
Abstract
Human immunodeficiency virus (HIV) populations are characterized by extensive genetic diversity. Antigenic diversification is essential for escape from immune selection and therapy, and remains one of the major obstacles for the development of an efficient vaccine strategy. Even if intensive efforts have been made for understanding the molecular mechanisms responsible for genetic diversity in HIV, conclusive data in vivo is still lacking. Recent works have addressed this issue, focusing on the identification of the sources of genetic diversity during in vivo infections and on the estimate of the pervasiveness of genetic recombination during replication in vivo. Surprisingly, it appears that despite the error-prone nature of the viral polymerase, the bulk of mutations found in patients are indeed due to the effect of a cellular restriction factor. This factor tends to hypermutate the viral genome abolishing viral infectivity. When hypermutation is incomplete, the virus retains infectivity and converts the effect of the cellular factor to its advantage by exploiting it to generate genetic diversity that is beneficial for viral propagation. This view contrasts the long-standing dogma that viral diversity is due to the intrinsic error-prone nature of the viral replication cycle. Besides hypermutations and mutations, recombination is also a pervasive source of genetic diversity. The estimate of the frequency at which this process takes place in vivo has remained elusive, despite extensive efforts in this sense. Now, using single genome amplification, and starting from publically available datasets, it has been obtained a confirmation of the estimates previously made using tissue culture studies. These recent findings are presented here and their implications for the development of future researches are discussed.
Highlights
Main text A large number of studies have measured viral mutation rates in cell culture [1, 2]. These studies have pointed to a critical role of the viral reverse transcriptase (RT) enzyme in generating mutations, leading to the idea that RT is the dominant producer of genetic diversity
(1) Do hypermutated non-infectious genomes serve as reservoirs for rescuing mutations by superinfecting viruses through recombination, extending the sequence space explored by the virus? (2) What is the relevance of the differences in the level of expression of A3G in the different cell types for sequence diversification at the level of transmission? The limited number of viruses transmitted during primary infections forces the viral population through a bottleneck from which genetic diversification must be re-established
Do the various cell types infected during spreading in the organism introduce sequence diversification at different paces depending on the stage and tissue infected? (3) What is the profile of APOBEC proteins expression in elite-controllers and long-term non-progressors? Do some individuals show differences in Human immunodeficiency virus (HIV) mutation rates? Are differences more related to host genetic or to the viral genotype? (4) Are other nucleic acids editing enzymes involved in controlling genetic diversity? (5) What is the implication of the genome in modulating sequence diversity? Another recent work [8], indicates that the frequency of generation of sequence divergence is not homogeneous along the HIV-1 env gene
Summary
Viral genetic diversity is essential for escape from immune selection and therapy, and remains one of the major obstacles to the eradication of the immunodeficiency virus (HIV). The mechanisms of HIV genetic diversification are well understood in vitro and in cell culture models, in vivo data has been lacking. A recent burst of papers lead us one step closer to understanding these mechanisms in vivo. We discuss the main findings described in these works that shed new light on the mechanisms fostering HIV genetic diversity in vivo
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
