Variation in Intra-individual Lentiviral Evolution Rates: a Systematic Review of Human, Nonhuman Primate, and Felid Species

Abstract

Lentiviral replication mediated by reverse transcriptase is considered to be highly error prone, leading to a high intra-individual evolution rate that promotes evasion of neutralization and persistent infection. Understanding lentiviral intraindividual evolutionary dynamics on a comparative basis can therefore inform research strategies to aid in studies of pathogenesis, vaccine design, and therapeutic intervention. We conducted a systematic review of intra-individual evolution rates for three species groups of lentiviruses-feline immunodeficiency virus (FIV), simian immunodeficiency virus (SIV), and human immunodeficiency virus (HIV). Overall, intra-individual rate estimates differed by virus but not by host, gene, or viral strain. Lentiviral infections in spillover (nonadapted) hosts approximated infections in primary (adapted) hosts. Our review consistently documents that FIV evolution rates within individuals are significantly lower than the rates recorded for HIV and SIV. FIV intra-individual evolution rates were noted to be equivalent to FIV interindividual rates. These findings document inherent differences in the evolution of FIV relative to that of primate lentiviruses, which may signal intrinsic difference of reverse transcriptase between these viral species or different host-viral interactions. Analysis of lentiviral evolutionary selection pressures at the individual versus population level is valuable for understanding transmission dynamics and the emergence of virulent and avirulent strains and provides novel insight for approaches to interrupt lentiviral infections. IMPORTANCE To the best of our knowledge, this is the first study that compares intra-individual evolution rates for FIV, SIV, and HIV following systematic review of the literature. Our findings have important implications for informing research strategies in the field of intra-individual virus dynamics for lentiviruses. We observed that FIV evolves more slowly than HIV and SIV at the intra-individual level and found that mutation rates may differ by gene sequence length but not by host, gene, strain, an experimental setting relative to a natural setting, or spillover host infection relative to primary host infection. KEYWORDS evolution rate, feline immunodeficiency virus, human immunodeficiency virus, lentivirus, simian immunodeficiency virusA characteristic feature of lentiviruses is a high rate of molecular evolution relative to those of other viruses and parasites (1). Low fidelity of lentiviral reverse transcriptase (RT) during DNA synthesis leads to the accumulation of mutations, resulting in intra-host viral variants, often termed quasispecies (2-4). The accumulation of numerous mutations, especially in antigens targeted by neutralizing antibodies or therapeutic agents, is thought to provide a mechanism for immune escape and enhance the risk of disease progression (5).

Decreased Sensitivity of the Serological Detection of Feline Immunodeficiency Virus Infection Potentially Due to Imported Genetic Variants

“…TM is the immunodominant epitope in FIV that induces the earliest and strongest antibody response in cats experimentally infected with FIV [53,62,63,71,72]. Although the evolutionary rate of FIV is rather slow when compared to other lentiviruses [85] and seems to be dependent on the virus strain and the infection stage [86], it has been shown that the preferred genetic location for recombination is in the envelope ( env ) gene, which also encodes TM [10,25,61,87]. Additionally, low fidelity in the transcription process and a change in the clade distribution could have contributed to the increased variability of this protein.…”

Interests of the Non-Human Primate Models for HIV Cure Research

“…Historically, feline models using cats infected with immunodeficiency virus (FIV) also served as models of naturally occurring immunodeficiency [ 29 ]. However, because FIV infection does not reproduce all the features of HIV infection and some important aspects differ markedly between cats and humans, this model is rarely used [ 4 , 30 ]. Mice, rats, or rabbits were originally proposed, but they could not be successfully infected with HIV [ 4 , 31 , 32 ].…”

Early sample tagging and pooling enables simultaneous SARS-CoV-2 detection and variant sequencing

“…ApharSeq utilizes sequencing for the detection of viral molecules, and as such it is well suited to variant calling. A common hurdle in amplicon-based genotyping assays, especially in the case of viruses that might manifest multiple minor variants in the same host, is the inability to distinguish between PCR and sequencing errors from underlying genotype variants (32,33). Unlike other common viral genome sequencing protocols (34,35), ApharSeq incorporates a unique molecular identifier (UMI) at the reverse transcription step.…”