Memory in Retroviral Quasispecies: Experimental Evidence and Theoretical Model for Human Immunodeficiency Virus

Here we show, at a high resolution (1%), the human immunodeficiency virus type 1 (HIV-1) protease gene quasispecies landscape from three infected naïve individuals. A huge range of genetic configurations was found (67%, 71%, and 80% of the nucleotide clones from the three individuals, respectively, were different), and these configurations created a dense net that linked different parts of the viral population. Similarly, a vast diversity of different protease activities was also found. Importantly, 65% of the analyzed enzymes had detectable protease activity, and 11% of the minority individual variants showed similar or better fitness than the master (most abundant) enzyme, suggesting that the viral complexity in this genomic region does not exclusively depend on the enzyme's catalytic efficiency. Several high-fitness minority variants had only one substitution compared to the master sequence, supporting the possibility that the rugged HIV-1 protease quasispecies fitness landscape may be formed by a continuous network that can be traversed by single mutational steps without passing through defective or less-adapted proteins.

Section: Figsupporting

confidence: 55%

Fitness Landscape of Human Immunodeficiency Virus Type 1 Protease Quasispecies

Fernàndez

Clotet

Martı́nez

2007

“…Nevertheless, for the first time we reveal that subgenotype Ae/A2 sequences remain present in the leukocytes in our population. This observation is remarkably similar to the archiving of the fittest ancestral HIV sequences in different cellular or anatomical compartments independently of the viral genotypes dominant in the serum, a phenomenon defined as cellular or anatomical memory (6). In this study, we could not detect subgenotype Ae/A2 even after the clonal analysis of serum HBV isolates (the assay was sensitive enough to detect viral subpopulations as low as 8 to 10%), but it might be possible that subgenotype Ae/A2 circulates in a very small proportion of the sera that remains untraceable, either due to the sensitivity of the assay used or the predominating effect of other genotypes in the sera, similarly to the phenomenon previously explained in the case of HCV (32).…”

Section: Discussionmentioning

confidence: 56%

Genetic Characterization of Hepatitis B Virus in Peripheral Blood Leukocytes: Evidence for Selection and Compartmentalization of Viral Variants with the Immune Escape G145R Mutation

Datta

Panigrahi

Biswas

et al. 2009

The compartmentalization of viral variants in distinct host tissues is a frequent event in many viral infections. Although hepatitis B virus (HBV) classically is considered hepatotropic, it has strong lymphotropic properties as well. However, unlike other viruses, molecular evolutionary studies to characterize HBV variants in compartments other than hepatocytes or sera have not been performed. The present work attempted to characterize HBV sequences from the peripheral blood leukocytes (PBL) of a large set of subjects, using advanced molecular biology and computational methods. The results of this study revealed the exclusive compartmentalization of HBV subgenotype Ae/A2-specific sequences with a potent immune escape G145R mutation in the PBL of the majority of the subjects. Interestingly, entirely different HBV genotypes/subgenotypes (C, D, or Aa/A1) were found to predominate in the sera of the same study populations. These results suggest that subgenotype Ae/A2 is selectively archived in the PBL, and the high prevalence of G145R indicates high immune pressure and high evolutionary rates of HBV DNA in the PBL. The results are analogous to available literature on the compartmentalization of other viruses. The present work thus provides evidence in favor of the compartment-specific abundance, evolution, and emergence of the potent immune escape mutant. These findings have important implications in the field of HBV molecular epidemiology, transmission, transfusion medicine, organ transplantation, and vaccination strategies.

“…VIRAL EMERGENCE BY GENOME REPLACEMENT 6667 on May 9, 2018 by guest http://jvi.asm.org/ represent the complete loss of resistant mutants, and memory genomes survive at a frequency that is high enough to promote a rapid rebound of resistance when treatment is resumed (2). Note that in this case, there are two types of memory, the cellular memory and the replicative memory.…”

Section: Vol 81 2007mentioning

confidence: 99%

Emergence of Mammalian Cell-Adapted Vesicular Stomatitis Virus from Persistent Infections of Insect Vector Cells

Novella

Ebendick-Corpus

Zárate

et al. 2007

Arboviruses (arthropod-borne viruses) represent quintessential generalists, with the ability to infect and perform well in multiple hosts. However, antagonistic pleiotropy imposed a cost during the adaptation to persistent replication of vesicular stomatitis virus in sand fly cells and resulted in strains that initially replicated poorly in hamster cells, even when the virus was allowed to replicate periodically in the latter. Once a debilitated strain started replicating continuously in mammalian cells, fitness increased significantly. Fitness recovery did not entail back mutations or compensatory mutations, but instead, we observed the replacement of persistence-adapted genomes by mammalian cell-adapted strains with a full set of new, unrelated sequence changes. These mammalian cell-adapted genomes were present at low frequencies in the populations with a history of persistence for up to a year and quickly became dominant during mammalian infection, but coexistence was not stable in the long term. Periodic acute replication in mammalian cells likely contributed to extending the survival of minority genomes, but these genomes were also found in strictly persistent populations.The molecular mechanisms underlying adaptation are one of the most crucial topics of evolutionary genetics. In the case of viruses, this question is also important because adaptation will have an impact on transmission and on the pathogenesis caused by infection and, thus, on our ability to control viral diseases (6). Adaptation of a viral population to a novel environment occurs when variants with higher fitness become dominant in the population. The source of those variants depends on the evolutionary history of the strain. Viruses with a history of bottlenecks usually have low fitness, and their recovery takes place because of beneficial variation during replication in the form of reversion or compensation, resulting in the accumulation of mutations in those unfit genomes (9,19). In viruses that undergo homologous recombination, adaptation may be further favored because recombination may bring two or more beneficial mutations together in a single genome (3). A second mechanism that results in viruses that are unfit in a particular environment is trade-off, when adaptation to one environment results in maladaptation to a second environment. There are two situations that exemplify maladaptation due to trade-offs. First, arbovirus adaptation to insect cells sometimes results in populations that have low fitness in mammalian cells (5, 10, 33). Second, antibody escape and drug-resistant mutants usually have low fitness in the absence of the selective pressure (18,20,22,25). We have used vesicular stomatitis virus (VSV) to study how low-fitness viral populations recover when maladaptation is the result of trade-offs.VSV is the prototype of the Rhabdoviridae family (24). Its genome is a molecule of single-stranded, negative-sense RNA that codes for at least five proteins. The nucleoprotein (N) encapsidates the viral genome; the phosphoprotein ...