PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “HIV evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed2017

A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line.

A directed evolution approach was used to select for Adeno-associated virus (AAV) capsids that would exhibit more tropism toward an HIV-1 producer T cell line with the long-term goal of developing improved gene transfer vectors. A library of AAV variants was used to infect H9 T cells previously infected or uninfected by HIV-1 followed by AAV amplification with wild-type adenovirus. Six rounds of biological selection were performed, including negative selection and diversification after round three. The H9 T cells were successfully infected with all three wild-type viruses (AAV, adenovirus, and HIV-1). Four AAV cap mutants best representing the small number of variants emerging after six rounds of selection were chosen for further study. These mutant capsids were used to package an AAV vector and subsequently used to infect H9 cells that were previously infected or uninfected by HIV-1. A quantitative polymerase chain reaction assay was performed to measure cell-associated AAV genomes. Two of the four cap mutants showed a significant increase in the amount of cell-associated genomes as compared to wild-type AAV2. This study shows that directed evolution can be performed successfully to select for mutants with improved tropism for a T cell line in the presence of HIV-1.

Capsid↗
PubMedDate not supplied

Mechanistic features of recombination in HIV.

The importance of recombination in retroviral evolution has been acknowledged for several decades. Consequently, after the identification of HIV as the etiological agent of AIDS, it was suspected that recombination could also play a central role in the evolution of this virus. However, only recently, extensive epidemiologic studies of HIV infections worldwide have provided an estimate for the occurrence of recombination in vivo, unveiling recombination frequencies that dwarf those initially expected. Nowadays, recombination is regarded as an integral part of the infectious cycle of this retrovirus, which impacts on diagnosis and treatment of infections, especially when genetically distant viruses have been at the origin of the recombinant forms. Retroviral recombination is observed when two genetically divergent genomic RNA molecules are present in the same viral particle, and arises during the reverse transcription step. This review focuses on the mechanisms that have been proposed to account for the occurrence of recombination in retroviruses, from the strand displacement model, according to which recombination occurs during second DNA strand synthesis; to the description of the factors responsible for copy-choice recombination during first DNA strand synthesis, such as the presence of breaks, pause sites, or secondary structures in the genomic RNA. Most of these models have been supported by experimental data obtained from in vitro reconstituted systems or from cell infection studies using academic model sequences. The situation in vivo is expected to be more complex, since several factors come into play when recombination involves relatively distant isolates, as in the case of inter-subtype recombination. At present, it is clear that further studies are needed in order to evaluate whether a prevailing mechanism exists for in vivo recombination, and these studies will also be essential for understanding how the underlying mechanisms of recombination contribute to the evolution of HIV.

Evolution, Molecular↗
PubMed1990

[Evolution of the definition of AIDS. The main classifications of HIV infection].

The purpose of this paper is to trace the evolution of AIDS definition and describe the principal classification systems of HIV infection as defined since 1981. Our work is principally based on data from the American Centers of Disease Control on the one hand (clinical evaluation of infection stage) and from the Walter Reed Institute (immunological evaluation of infection stage) on the other hand. To describe this disease with multiple aspects the separate use of these two classification systems does not provide a thorough evaluation of the patient's condition. Non consensus had been reached to date, although an agreement on this matter would foster an important epidemiological and therapeutic progress in both adult and childhood patients.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[Human immunodeficiency virus and AIDS in terms of reverse transcriptase and molecular evolution].

Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in the host. The computer analysis of the HIV-1 genome has shown that the mutation manner is dependent on oligonucleotide sequences (in particular, six bases long); thus HIV-1 adaptively evolves. The six-base-long interaction between template-primer oligonucleotide and the reverse transcriptase (RT) has been revealed by the crystal structure of RT, in vitro termination assay of plymerization, and hydroxyl radical footprint analysis. It has been thought that AIDS is caused by the large numbers of HIV-1 quasispecies yielded by the adaptive and rapid evolution in the host. However, the slow evolution and the high levels of viral RNA in the progressive HIV-1 infected individuals (progressives) were recently reported; in contrast, the adaptive and rapid evolution and the low viral-RNA levels were reported in the non-progressives. This suggests that the physiological environment, e.g. pH and dNTP balance, in which RT works in the progressives is different from that in the non-progressives.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Each genomic RNA in HIV-1 heterozygous virus generate new virions.

Retrovirus are unique because they present two complete copies of the genomic RNA in each virion. It is believed that only one proviral DNA is formed from the two genomic RNAs. To check this hypothesis, we constructed two deleterious HIV-1 variants in gag gene which upon transfection in Cos-1 cells were able, by complementation, to form heterozygous viruses, used to infect MT4 cells in a plaque assay. Analysis of the proviral DNA of the eight plaques obtained indicated that five were recombinants between the two deleterious mutants. Three other plaques showed three bands corresponding to the reverse transcription of both strands of one heterozygous virion and to the recombination of the two genomes. These results demonstrate that the two genomic RNAs in HIV-1 heterozygous virions could be used in the generation of new viruses. This mechanism permits the recovery of deleterious mutants and enhances the evolutive potential of HIV-1.

Amino Acid Sequence↗
PubMed2006

Role of HIV-1 minority populations on resistance mutational pattern evolution and susceptibility to protease inhibitors.

We investigated, in the protease and GAG cleavage sites, the role of minority populations on the evolution of resistance to a subsequent boosted protease inhibitor (PI) regimen after a first failure to nelfinavir. Two pathways were observed: the addition of mutations to a currently dominant genotype when minority variants are not shown, or the emergence of a minority variant as a dominant strain. These minor species, not detected by standard genotype, may influence PI susceptibility.

Drug Resistance, Multiple, Viral↗
PubMed2004

Thirteen years HIV-1 sentinel surveillance and indicators for behavioural change suggest impact of programme activities in south-west Tanzania.

OBJECTIVE: To describe the evolution of the HIV-1 epidemic among women attending antenatal clinics in four different geographic areas within two rural regions with differing intervention intensity in south-west Tanzania. DESIGN AND METHODS: Age-specific trends in HIV-1 seroprevalence among antenatal clinic attendees in four distinct geographic areas of Mbeya region between 1988 and 2000 and in one area of Rukwa region between 1991 and 1999 were analysed and compared. In Mbeya region a comprehensive AIDS control programme has been implemented since 1988. Indicators measuring behavioural change and the attendance rate of patients with sexually transmitted diseases (STDs) were monitored through the established routine system, complemented by two Knowledge, Attitude and Practise (KAP) surveys in 1995 and 1999. RESULTS: Data showed an increasing HIV-1 prevalence from 1988 up to 1994/95 for women in the age group 15-24 years across all strata. Between 1994/95 and 2000 the prevalence declined significantly in all strata for this age group in Mbeya region with diverse patterns in spread of the infection accompanied by a significant decrease in the positive syphilis serology, high rate of condom use, significant delay of age for the start of sexual activity of primary school pupils and a high treatment rate for STDs. The increasing trend of the HIV-1 prevalence in Rukwa region continued. CONCLUSION: Declining trends of HIV-1 prevalence among women aged 15-24 years may correspond to a reduced incidence partially attributable to changes in behaviour and reduction of a biological factor influencing HIV-1 transmission to which the implemented programme could contribute.

Adolescent↗
PubMed2003

First demonstration of a lack of viral sequence evolution in a nonprogressor, defining replication-incompetent HIV-1 infection.

It is universally acknowledged that genetic diversity is a hallmark of HIV-1 infection, and it is one of the traits that has considerably hampered the development of an effective vaccine. In a study of full-length HIV-1 genomic sequences (>9 kb), we show unique evidence for complete absence of viral evolution in an individual with truly nonprogressive infection. Gross gene defects were not detected, but the state of replication incompetence was attributed to the presence of stop codons in the structural genes gag p17 and p24 and in pol RT, which emerged as a consequence of G-A hypermutation. These inactivating mutations may have occurred early, soon after infection, during the clonal stage of primary viral replication, since these are the sole archival strains present today. This genetic homogeneity, with <1% variation between strains over an 8-year period, suggests that only limited proviral integration events occurred in this patient. Further study on the antigenic properties of this strain may assist in the development of HIV vaccines and therapeutics.

Amino Acid Sequence↗
PubMed1999

Genealogical evidence for positive selection in the nef gene of HIV-1.

The pattern and process of evolution in the nef gene of HIV-1 was analyzed within and among patients. Using a maximum likelihood method that allows for variable intensity of selection pressure among codons, strong positive selection was detected in a hemophiliac patient over 30 mo of infection. By reconstructing the process of allele substitution in this patient using parsimony, the synapomorphic amino acid changes separating each time point were found to have high probabilities of being under positive selection, with selective coefficients of at least 3.6%. Positive selection was also detected among 39 nef sequences from HIV-1 subtype B. In contrast, multiple pairwise comparisons of nonsynonymous and synonymous substitution rates provided no good evidence for positive selection and sliding window analyses failed to detect most positively selected sites. These findings demonstrate that positive selection is an important determinant of nef gene evolution and that genealogy-based methods outperform pairwise methods in the detection of adaptive evolution. Mapping the locations of positively selected sites may also be of use in identifying targets of the immune response and hence aid vaccine design.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[The neuropsychic manifestations of HIV infection in children].

The authors analyse the frequency, the significance for prognosis and the localisation of the neuropsychological manifestation concerning the steps of evolution of the HIV infection in children. The pathogenetic aspects, the principal histopathological lesions and clinical corresponding aspects are also presented. The text refers to the modern neuroimaging investigations and to the new treatment possibilities.

AIDS Dementia Complex↗
PubMed2004

A statistical characterization of consistent patterns of human immunodeficiency virus evolution within infected patients.

Within-patient HIV populations evolve rapidly because of a high mutation rate, short generation time, and strong positive selection pressures. Previous studies have identified "consistent patterns" of viral sequence evolution. Just before HIV infection progresses to AIDS, evolution seems to slow markedly, and the genetic diversity of the viral population drops. This evolutionary slowdown could be caused either by a reduction in the average viral replication rate or because selection pressures weaken with the collapse of the immune system. The former hypothesis (which we denote "cellular exhaustion") predicts a simultaneous reduction in both synonymous and nonsynonymous evolution, whereas the latter hypothesis (denoted "immune relaxation") predicts that only nonsynonymous evolution will slow. In this paper, we present a set of statistical procedures for distinguishing between these alternative hypotheses using DNA sequences sampled over the course of infection. The first component is a new method for estimating evolutionary rates that takes advantage of the temporal information in longitudinal DNA sequence samples. Second, we develop a set of probability models for the analysis of evolutionary rates in HIV populations in vivo. Application of these models to both synonymous and nonsynonymous evolution affords a comparison of the cellular-exhaustion and immune-relaxation hypotheses. We apply the procedures to longitudinal data sets in which sequences of the env gene were sampled over the entire course of infection. Our analyses (1) statistically confirm that an evolutionary slowdown occurs late in infection, (2) strongly support the immune-relaxation hypothesis, and (3) indicate that the cessation of nonsynonymous evolution is associated with disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Hospitalization for HIV infection in public hospitals in Paris. Recent evolution (1988-1990) and short-term projections (1991-2)].

Acute-care hospitalization of subjects infected with HIV in Parisian public hospitals (Assistance Publique-Hôpitaux de Paris) increased by 10% between 1988 and 1990, while outpatient day-care rose by 73%. During this time, the percentage of patients coming from the Paris suburbs rose from 30 to 35%. The average length of stay increased from 14.2 to 14.9 days during the same period, and hospital stays lasting longer than 30 days (9.2%) accounted for 39.2% of all hospitalizations. Forecasts for 1991 and 1992 show acute-care hospitalization rising from 25 to 30% and outpatient care increasing from 45 to 94%, depending upon the hypothesis considered.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Intrapatient diversity and its correlation with viral setpoint in human immunodeficiency virus type 1 CRF02_A/G-IbNG infection.

The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the disease-free interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1/-/log(10) copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P = 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P = 0.01). Greater nucleotide (P = 0.015) and amino acid (P = 0.048) divergences and a greater nucleotide divergence rate (P = 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.

Base Sequence↗
PubMed2005

Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection.

HIV type 1 (HIV-1) can rapidly escape from neutralizing antibody responses. The genetic basis of this escape in vivo is poorly understood. We compared the pattern of evolution of the HIV-1 env gene between individuals with recent HIV infection whose virus exhibited either a low or a high rate of escape from neutralizing antibody responses. We demonstrate that the rate of viral escape at a phenotypic level is highly variable among individuals, and is strongly correlated with the rate of amino acid substitutions. We show that dramatic escape from neutralizing antibodies can occur in the relative absence of changes in glycosylation or insertions and deletions ("indels") in the envelope; conversely, changes in glycosylation and indels occur even in the absence of neutralizing antibody responses. Comparison of our data with the predictions of a mathematical model support a mechanism in which escape from neutralizing antibodies occurs via many amino acid substitutions, with low cross-neutralization between closely related viral strains. Our results suggest that autologous neutralizing antibody responses may play a pivotal role in the diversification of HIV-1 envelope during the early stages of infection.

Adult↗
PubMed2001

A long-term follow-up of an HIV type 1-infected patient reveals a coincidence of Nef-directed cytotoxic T lymphocyte effectors and high incidence of epitope-deleted variants.

Cytotoxic T lymphocytes (CTL) play a critical role in controlling human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) infections. However, in spite of developing a strong CTL response most HIV-1-infected patients eventually progress to AIDS. Amino acid changes in CTL epitope have been previously described and may permit HIV to escape from CTL immune responses. The importance of CTL selection pressure in controlling the course of viral evolution in HIV-infected patient remains debatable. For over a 10-year period, we longitudinally followed a patient for bulk unstimulated effector (eCTL) and stimulated memory CTL responses (mCTL) against the viral proteins Gag, Pol, and Nef. The patient showed a strong CTL response against Nef in unstimulated peripheral blood mononuclear cells with a peak during Month 40 of the follow-up. The mCTL response was also higher against Nef than Gag and Pol. PCR amplification and nucleotide sequencing of the plasma viral variants showed a viral variant with the epitope deletion that was detected early during the follow-up and essentially replaced the wild-type virus during the peak eCTL response. These studies support the importance of Nef epitope deletion as a mechanism for HIV-1 escape from CTL immune pressure.

Amino Acid Sequence↗
PubMed2006

Evolutionary history of HIV-1 subtype B and F infections in Brazil.

OBJECTIVE: To reconstruct the onset date of the HIV-1 B and F epidemics in Brazil based on virus diversification over time. DESIGN: We studied HIV-1 env V3 sequences (210 nt) with a known sampling year isolated from HIV-1 positive patients from Brazil between 1989 and 1997: 101 subtype B sequences and 41 subtype F sequences. METHODS: HIV-1 V3 env sequences were grouped by year of collection and the relationship between the sampling years of HIV-1 sequences and their genetic distance to the reconstructed common ancestor (intra-population divergence) or to other sequences from the same year (intra-population diversity) was examined by using linear regression analysis. RESULTS: Regression analysis of nucleotide distances, revealed a highly significant positive correlation between sampling years of subtype B and F V3 sequences and their intra-population divergence (P < 0.001) or diversity (P < 0.0001). In both subtype populations, the divergence and diversity increased at a rate of 0.5 and 0.9% per year, respectively. Considering these evolutionary rates, we estimate the onset of the subtype B and F HIV-1 epidemics in Brazil during early 1970s and early 1980s, respectively. CONCLUSIONS: The consistent correlation between divergence and diversity of the V3 sequences with their sampling years indicates that the molecular clock is operational in the evolution of the HIV-1 in Brazil's epidemic, and show that subtypes B and F are evolving at a similar rate over time. The dating results suggest a discontinuous introduction of these subtypes in the Brazilian population.

Brazil↗
PubMed1996

Evidence for limited within-person evolution of the V3 domain of the HIV-1 envelope in the amsterdam population.

OBJECTIVE: To study the development of the V3 region of the HIV-1 envelope over time, both within subjects and population-wide. METHODS: Direct V3 sequences were obtained from viral RNA from seroconversion samples of 138 individuals [32 intravenous drug users (IVDU), 106 homosexual men], as well as from 5-year follow-up samples of 45 of these individuals (11 IVDU, 34 homosexual men). RESULTS: The population-wide variation of the V3 region in both the seroconversion samples and the 5-year samples steadily increased over consecutive years and were of similar magnitude in each calendar year. The variation in the IVDU group was slightly lower (presumably lagging behind) than in the homosexual group, but also increased over time. The consensus sequence, representing the centre of the swarm of variants, remained almost stationary in 10 years of evolution. The V3 sequences from virions in serum collected 5 years after seroconversion still resembled those from the seroconversion sample, either in overall similarity or in specific (signature) amino acids. Seroconversion and late sequences from a donor-recipient pair were also very similar. CONCLUSIONS: The variation in V3 sequences from seroconversion samples is as large as that in 5-year follow-up samples from the same calendar year, suggesting that there is no strong selection for a particular V3 genotype at transmission. The HIV-1 subtype B quasispecies in a naive population appears to evolve through unbiased expansion around a stationary consensus sequence. Despite its large variability, the V3 region retains many of its individual characteristics after 5 years of infection. This indicates that the sampling moment (relative to the seroconversion data) will not greatly influence the results of phylogenetic analyses.

Base Sequence↗