Evolutionary and immunological implications of contemporary HIV-1 variation

Korber, Bette T.; Gaschen, Brian; Yusim, Karina; Thakallapally, Rama; Keşmir, Can; Detours, Vincent

doi:10.1093/bmb/58.1.19

Cited by 457 publications

(367 citation statements)

References 115 publications

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“…This observation indicates that the potency of the selective pressure exerted by neutralizing antibodies can account for the extensive variability of env in comparison to other HIV genes (31). The question then arises why such a strong selective pressure fails to appreciably impact levels of virus replication as does chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Rapid evolution of the neutralizing antibody response to HIV type 1 infection

Richman¹,

Wrin²,

Little³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

1,083

1,088

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A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0 -39 months) autologous viruses, whereas responses to laboratory and heterologous primary strains were often lower and delayed. Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.

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Section: Discussionmentioning

confidence: 99%

Rapid evolution of the neutralizing antibody response to HIV type 1 infection

Richman¹,

Wrin²,

Little³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

1,083

1,088

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“…36 The use of the consensus sequence is justified by the shortest distances between this 'average' and individual isolate sequences. 37 In addition, the HLA-A*6802-restricted CTL epitope DTVLEDINL from HIV pol was inserted, which was associated with long-term nonprogression. 38 Also incorporated were a Plasmodium berghei-derived epitope SYIPSAEKI, Amino-acid sequence of the RENTA polyprotein was compared with proteins in the available databases.…”

Section: Design Of the Renta Immunogenmentioning

confidence: 99%

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Nkolola

et al. 2004

Gene Ther

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For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA). Here, we describe engineering and preclinical development of a second immunogen RENTA, which will be used in combination with the present vaccine in a four-component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a fusion protein derived from consensus HIV clade A sequences of Tat, reverse transcriptase, Nef and gp41. We inactivated the natural biological activities of the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys broadening of HIVAelicited T-cell responses by a parallel induction of HIVA-and RENTA-specific responses recognizing multiple HIV epitopes.

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“…For example, genetic variation in a prey population can permit evolution that radically alters predator-prey dynamics (1,2), evolution in environmentally threatened populations can affect population recovery (3), and rapid evolution is now seen as a critical component shaping disease dynamics (e.g., in HIV, refs. [4][5][6][7]. Each of these discoveries was to some extent unexpected because, despite a growing number of examples of rapid evolution (8)(9)(10)(11), the default expectation has often continued to be that ecological and evolutionary dynamics occur on different time scales (12,13).…”

mentioning

confidence: 99%

Prey evolution on the time scale of predator–prey dynamics revealed by allele-specific quantitative PCR

Meyer

Ellner

Hairston

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

114

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Using rotifer-algal microcosms, we tracked rapid evolution resulting from temporally changing natural selection in ecological predator-prey dynamics. We previously demonstrated that predatorprey oscillations in rotifer-algal laboratory microcosms are qualitatively altered by the presence of genetic variation within the prey. In that study, changes in algal gene frequencies were inferred from their effects on population dynamics but not observed directly. Here, we document rapid prey evolution in this system by directly observing changes in Chlorella vulgaris genotype frequencies as the abundances of these algae and their consumer, Brachionus calyciflorus, change through time. We isolated a group of algal clones that we could distinguish by using microsatellite-DNA markers, and developed an allele-specific quantitative PCR technique (AsQ-PCR) to quantify the frequencies of pairs of clones in mixed culture. We showed that two of these genotypes exhibited a fitness tradeoff in which one was more resistant to predation (more digestion-resistant), and the other had faster population growth under limiting nitrogen concentrations. A fully specified mathematical model for the rotifer-algal population and evolutionary dynamics predicted that these two clones would undergo a single oscillation in clonal frequencies followed by asymptotic fixation of the more resistant clone, rather than the recurrent oscillations previously observed with other algal clones. We used AsQ-PCR to confirm this prediction: the superior competitor dominated initially, but as rotifer densities increased, the more predator-resistant clone predominated.Chlorella vulgaris ͉ clonal models ͉ evolutionary tradeoff ͉ grazing resistance ͉ rapid evolution T here has been an increasing appreciation during the past three decades that ecological and evolutionary dynamics can operate on similar time scales and interact in important ways. For example, genetic variation in a prey population can permit evolution that radically alters predator-prey dynamics (1, 2), evolution in environmentally threatened populations can affect population recovery (3), and rapid evolution is now seen as a critical component shaping disease dynamics (e.g., in HIV, refs. 4-7). Each of these discoveries was to some extent unexpected because, despite a growing number of examples of rapid evolution (8-11), the default expectation has often continued to be that ecological and evolutionary dynamics occur on different time scales (12, 13). Although recent discoveries challenge this notion (e.g., refs. 14-16), direct demonstrations of the mechanistic interplay between genetic change and ecological process remain rare. Here, we present a clear demonstration of prey evolution in concert with temporal changes in predator and prey densities, using genetic markers to quantify the evolutionary dynamics.Laboratory microcosms of rapidly reproducing interacting species have proven to be effective systems for the study of simultaneous ecological and evolutionary dynamics (17), including consumer-vic...

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Evolutionary and immunological implications of contemporary HIV-1 variation

Cited by 457 publications

References 115 publications

Rapid evolution of the neutralizing antibody response to HIV type 1 infection

Rapid evolution of the neutralizing antibody response to HIV type 1 infection

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Prey evolution on the time scale of predator–prey dynamics revealed by allele-specific quantitative PCR

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