HIV-1 V3 domain variation in brain and spleen of children with AIDS: Tissue-specific evolution within host-determined quasispecies

Epstein, Leon G.; Kuiken, Carla; Blumberg, Benjamin M.; Hartman, Susan; Sharer, Leroy R.; Clement, Marjon J.; Goudsmit, Jaap

doi:10.1016/0042-6822(91)90072-j

Cited by 196 publications

(124 citation statements)

References 31 publications

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“…Extensive temporal and topographical genetic variations are observed in human immunodeficiency virus type 1 (HIV-1) populations in different individuals and also in those present within the same individual Epstein et al, 1991 ;Delassus et al, 1992;Ball et al, 1994). The structural genes of HIV-1 differ in their levels of genetic variation, with the gag and pol genes being more conserved than the env gene (Myers et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 observed during zidovudine (AZT) therapy

Sheehy

Desselberger²,

Whitwell³

et al. 1996

Journal of General Virology

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Nucleotide sequences of regions of the envelope (env) and polymerase (po/) genes of human immunodeficiency virus type 1 (HIV-1) proviral DNA were obtained from sequential blood and autopsy samples from an AIDS patient who had been treated with zidovudine for 9 months, Phylogenetic analyses showed that a reduction in genetic heterogeneity of the env regions of viruses present in the proviral blood population occurred during therapy, and this coincided with an increased pol gene heterogeneity. Differences were observed in different organs obtained post mortem for both the env and pol coding regions. The cardiac blood proviral population consisted mainly of variants which possessed sequences containing mutations at position 215 of the pol gene, associated with drug resistance. By contrast, the brain population consisted entirely of zidovudine sensitive genotypes, and this organ also harboured variants with genetically distinct env sequences. The lymph tissues obtained after death held more diverse proviral env and pol populations, containing both zidovudine sensitive and resistant genotypes.

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Section: Introductionmentioning

confidence: 99%

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 observed during zidovudine (AZT) therapy

Sheehy

Desselberger²,

Whitwell³

et al. 1996

Journal of General Virology

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“…Although many models of HIV-1 evolution assume that the population of infected cells within the host is well-mixed (28,30), there is direct evidence that this is an unrealistic assumption. On a macroscopic spatial scale, it has been recognized for some time that HIV genetic variability is spatially heterogeneous (31)(32)(33)(34)(35)(36). Studies of proviral clones isolated from individual splenic white pulps have revealed that such differentiation can also occur on a microscopic scale (37).…”

mentioning

confidence: 99%

Genetic drift and within-host metapopulation dynamics of HIV-1 infection

Frost

Dumaurier

Wain‐Hobson

et al. 2001

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

127

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Most HIV replication occurs in solid lymphoid tissue, which has prominent architecture at the histological level, which separates groups of productively infected CD4 ؉ cells. Nevertheless, current population models of HIV assume panmixis within lymphoid tissue. We present a simple ''metapopulation'' model of HIV replication, where the population of infected cells is comprised of a large number of small populations, each of which is established by a few founder viruses and undergoes turnover. To test this model, we analyzed viral genetic variation of infected cell subpopulations within the spleen and demonstrated the action of founder effects as well as significant variation in the extent of genetic differentiation between subpopulations among patients. The combination of founder effects and subpopulation turnover can result in an effective population size much lower than the actual population size and may contribute to the importance of genetic drift in HIV evolution despite a large number of infected cells.H IV has an enormous evolutionary potential because of the combination of a high mutation rate (Ϸ3 ϫ 10 Ϫ5 substitutions͞site͞generation; ref. 1), a short generation time (Ϸ2.6 days; refs. 2 and 3), and a large number of infected cells within the host (10 7 -10 8 infected cells; ref. 4). Many analyses of the pattern of nucleotide substitution in the viral env gene have detected evolution in response to positive selection (5-16), although relatively few studies have linked these patterns of viral genetic variation to selection by defined immune responses or for changes in viral phenotype associated with coreceptor usage. In the presence of antiretroviral agents that target viral protease and reverse transcriptase, positive selection has been described in numerous studies, which demonstrate convergent evolution in different individuals of mutations that confer drug resistance (17)(18)(19)(20). Although specific mutations have been identified with escape from immune responses and escape from antiretrovirals, viral genetic variation reflects more than just these focused positive selection pressures and may reflect more subtle processes of within-host competition between viruses for higher replicative potential.Despite an enormous potential to respond to selection, there can be substantial differences between infected individuals in the evolution of drug resistance. For example, the frequency of single drug-resistant mutants in viral protease and reverse transcriptase before therapy can vary dramatically between hosts (21-23), apparently by random. Indirect observations of the apparently stochastic way in which multiply resistant mutants emerge during therapy are also consistent with a role of genetic drift (18,24,25). In addition, three studies of the evolution of env gene sequences have found substantially lower genetic variation than expected for a population of the order of 10 7 (24,26,27). These studies estimated the ''effective'' population size to be of the order of 10 3 , reflecting the high relatedness be...

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“…As a consequence, the viral population will be structured at a hierarchy of levels, and this may impact both viral dynamics and evolution (Kepler and Perelson 1998;Kirschner et al 1998;Holt 2000). Genetic differentiation between HIV populations inhabiting different organs within the same infected patient has been documented (Epstein et al 1991), and this kind of tissue-level compartmentalization may also be relevant to the transmission of the pathogen among host organisms (Poss et al 1998;Wolinsky and Learn 1999, pp. 294-295).…”

Section: Generalizationsmentioning

confidence: 99%

Linking Dynamical and Population Genetic Models of Persistent Viral Infection

Kelly

Williamson²,

Orive³

et al. 2003

The American Naturalist

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This article develops a theoretical framework to link dynamical and population genetic models of persistent viral infection. This linkage is useful because, while the dynamical and population genetic theories have developed independently, the biological processes they describe are completely interrelated. Parameters of the dynamical models are important determinants of evolutionary processes such as natural selection and genetic drift. We develop analytical methods, based on coupled differential equations and Markov chain theory, to predict the accumulation of genetic diversity within the viral population as a function of dynamical parameters. These methods are first applied to the standard model of viral dynamics and then generalized to consider the infection of multiple host cell types by the viral population. Each cell type is characterized by specific parameter values. Inclusion of multiple cell types increases the likelihood of persistent infection and can increase the amount of genetic diversity within the viral population. However, the overall rate of gene sequence evolution may actually be reduced.

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HIV-1 V3 domain variation in brain and spleen of children with AIDS: Tissue-specific evolution within host-determined quasispecies

Cited by 196 publications

References 31 publications

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 observed during zidovudine (AZT) therapy

Concurrent evolution of regions of the envelope and polymerase genes of human immunodeficiency virus type 1 observed during zidovudine (AZT) therapy

Genetic drift and within-host metapopulation dynamics of HIV-1 infection

Linking Dynamical and Population Genetic Models of Persistent Viral Infection

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