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 1,189 records · Page 66Linked to original sources
PubMed1997

In vivo sequence variability of human immunodeficiency virus type 1 envelope gp120: association of V2 extension with slow disease progression.

According to the rate of depletion of CD4 cell counts, we grouped 12 cases of human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8 cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month) progressors and determined the individual viral quasispecies patterns by sequencing the genome region encoding the V1, V2, and V3 loops of envelope protein. Although the quasispecies structures varied widely from one individual to another, a strong correlation was observed between a low rate of disease progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2 loop extension was observed specifically in individuals with slow or no disease progression, whereas basic amino acid substitutions in V3 characteristic of a viral phenotype shift from non-syncytium inducing to syncytium inducing were observed in patients with advanced stages of disease regardless of their rate of disease progression. Studies with recombinant viruses suggested that elongation of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages. Thus, our results suggest the association of distinct sequence features of both V3 and V2 with particular patterns of disease progression. Elongation of the V2 loop may be a good predictor of slow disease progression, while basic substitutions of V3 without elongation of V2 are characteristic of rapid progression.

Amino Acid Sequence↗
PubMed1998

CCR5/delta(ccr5) heterozygosity: a selective pressure for the syncytium-inducing human immunodeficiency virus type 1 phenotype. NIAID AIDS Clinical Trials Group Protocol 241 Virology Team.

Mechanisms underlying the delay in dominance of syncytium-inducing (SI) phenotype HIV-1 (human immunodeficiency virus type 1) in vivo are unknown. Both random mutational events and selective pressures operative only late in the disease process have been suggested to underlie the shift from CCR5 to alternative coreceptor usage. Among the moderately advanced patients who entered AIDS Clinical Trials Group protocol 241, SI viral phenotype was more common among CCRS/delta(ccr5) heterozygotes (7/7, 100%) than among CCR5/CCR5 homozygotes (29/88, 33%; P < .001, Fisher's exact test). Other characteristics did not differ at study entry by CCR5 genotype, including median CD4 cell counts, plasma RNA levels, and infectious HIV-1 titers in circulating cells. These data indicate that CCR5/delta(ccr5) heterozygosity, which decreases cell-surface levels of CCR5 available to serve as an HIV-1 entry coreceptor, is a selective pressure for evolution of T cell line-tropic viruses that use an alternative coreceptor.

Adult↗
PubMed1993

Longitudinal study of EEG and evoked potentials in neurologically asymptomatic HIV infected subjects.

Serial electroencephalograms (EEGs) and multimodality evoked potentials (EPs) were performed along with neurological and neuropsychological evaluation, cerebrospinal fluid assessment and magnetic resonance imaging at 6 month intervals in 73 neurologically asymptomatic HIV infected subjects. The results were compared with 50 age- and sex-matched controls. EEG was abnormal in 2 subjects (3%) initially and was abnormal in 7 (9%) subjects by the last examination. EEG abnormality (diffuse slowing) correlated significantly with slowed reaction time in neuropsychological testing (P < 0.05). VEP and BAEP provided low yields of 1.3% and 4% respectively. SEP was abnormal in 7 (9%) of the subjects initially and in 10 (13%) subjects by the last testing, with 80% of the abnormalities seen on the posterior tibial study. In 3 subjects, initial SEP abnormalities predicted later development of myelopathy and peripheral neuropathy. Event-related auditory evoked potentials were performed in 39 subjects. They were abnormal in 5 subjects initially (12%) and in 6 subjects (15%) by the last examination and more commonly in advanced stages of the illness with lower T4 counts. This data shows the evolution and association of electrophysiological abnormalities in early HIV infection and suggests a predictive value for SEP in HIV infected asymptomatic individuals.

Adult↗
PubMed2005

Treatment response and drug resistance in patients infected with HIV type 1 group O viruses.

Information about the efficacy of antiretroviral drugs in HIV-1 group O strains as well on the virus evolution in terms of resistance development in vivo is very limited. We assessed the clinical, immunological, and virological response to antiretroviral therapy as well as the selection of drug resistance in six HIV-1 group O-infected patients. All but one initiated antiretroviral therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one protease inhibitor (PI). At baseline, median plasma HIV-1 group O RNA and CD4 counts were 32,256 (15,770-74,132) copies/ml and 88 cells/microl (13-170), respectively. Four patients reached undetectable plasma viremia 12 weeks after beginning treatment. However, viremia rebounded in one of them due to poor compliance. Another two patients had an initial reduction in plasma HIV-RNA greater than 1 log, but rebounded soon thereafter. At baseline, all patients' viruses revealed changes associated with NNRTI resistance (98G and 181C). Two out of three patients failing therapy developed resistance mutations. One selected changes M41L, E44D, D67N, V75M, M184V, and T215Y at the RT, and G48M, F53L, I54V, V82A, and L90M at the protease. Another selected mutations K70N, V75A, and M184V at the RT, and D30D/N and I84V at the protease while failing on indinavir. Interestingly, both patients showed a shift at codon 181 from C to Y, which might restore NNRTI susceptibility. Sustained viral suppression in HIV-1 group O-infected patients can be successfully achieved using antiretroviral regimens based on two NRTI and a boosted PI. Drug resistance mutations in HIV-1 group O seem to be selected at similar positions to those in HIV-1 group M viruses.

Adolescent↗
PubMed2004

Natural selection and the organ-specific differentiation of HIV-1 V3 hypervariable region.

The existence of organ-specific HIV-1 populations within infected hosts has been studied for many years; nonetheless results reported by different authors are somewhat discrepant. To tackle this problem, we used a population genetics approach to analyze previously published data from the V3 hypervariable region of the envelope env gene. Our results are compatible with a population subdivision by organs in 95% of individuals analyzed at autopsy. In addition, populations infecting the nervous system and testicles clearly appear as differentiated subsets of the so-called macrophage-tropic variants. Liver and kidney may harbor differentiated populations as well. Although it is widely accepted that organ compartmentalization arises as a consequence of different selective pressures imposed by different organs, a definitive demonstration has not yet been provided. Our analysis of the pattern of synonymous and nonsynonymous nucleotide substitutions provides evidence supporting this hypothesis, without discarding the role of other evolutionary processes. In contrast, positive selection does not seem to be the mechanism responsible for the evolution of patient-specific sequences.

Analysis of Variance↗
PubMed1996

Identification of multiple and distinct CD8+ T cell suppressor activities: dichotomy between infected and uninfected individuals, evolution with progression of disease, and sensitivity to gamma irradiation.

Using an in vitro model system that reflects the cellular interactions occurring in the microenvironment of lymphoid organs (i.e., the interaction between dendritic cells (DC) and CD4+ T lymphocytes), the ability of CD8+ T cells to inhibit HIV replication was investigated. DC, the most potent APC in the paracortical region of lymphoid organs, were cocultured with autologous, unstimulated CD4+ T cells resulting in viral replication in the absence of exogenous stimulation. Using two variations of DC cocultures, one an acute infection system and the other an endogenous infection system, two sets of activities were identified. One activity was expressed in both HIV-infected and -uninfected individuals, and a second was found only in HIV-infected individuals. These activities can be differentiated further by their evolution or lack thereof with disease progression in infected individuals and their sensitivity to gamma irradiation. Furthermore, the results indicate that CD8+ T cell modulation of HIV replication in CD4+ T cells is a multifactorial phenomenon involving both inhibitory and stimulatory effects on HIV replication.

CD4-Positive T-Lymphocytes↗
PubMed2005

Evolvability of the mode of peptide binding by an RNA.

The HIV Rev-response element (RRE) RNA binds strongly to two unrelated peptides, the HIV Rev peptide and an RRE-binding aptamer, the RSG-1.2 peptide, at a similar site, but using distinct sets of interactions. In this study, the nucleotide base requirements for the binding of the RRE to the Rev and RSG-1.2 peptides were determined by selection of Rev- and RSG-1.2-binding RRE variants using a bacterial reporter system. As a result, distinct differences in the bases necessary for binding the two peptides were found in the upper stem of the RRE. Strikingly, single nucleotide changes in this region were found to switch the peptide-binding specificity of the RRE from a bifunctional Rev- and RSG-1.2-binding mode to either a Rev-specific or a RSG-1.2- specific mode, demonstrating how an RNA can evolve alternative binding strategies in discrete steps without intermediate loss of function. This evolvability of the mode of peptide binding by an RNA presumably reflects the multidimensionality of conformational space that a given RNA has available for ligand recognition, which may have been utilized in the evolution of RNA-polypeptide complexes.

Electrophoresis, Polyacrylamide Gel↗
PubMed1999

Cells of the monocyte-macrophage lineage and pathogenesis of HIV-1 infection.

It is thought that monocyte-macrophages and probably dendritic cells play a central role in HIV-1 primary infection, as well as in its evolution, given that they are among the first cells infected and later function as important reservoirs for the virus. These cells may participate in the selection of certain viral strains instead of others. Levels of CCR5 coreceptor expression on the surface of monocytes and macrophages determine their susceptibility to infection by HIV-1 strains using this coreceptor and may explain, in part, the differences in the infectivity of these cells through the maturation process. However, selection for certain strains is not only determined by the level of coreceptor expression, but by the biochemical properties of the different coreceptors and their relationship with other surface molecules and the chemokine and cytokine networks, which also influence the selective viral infection and replication in these cells. Any current or newly designed therapies need to be evaluated, including careful analysis of the levels of HIV-1 infection of the cells of the monocyte-macrophage lineage, because these cells are both significant viral reservoirs and a center of virus production at all stages of the disease.

Cell Lineage↗
PubMed2001

[Osteonecrosis of the femoral head in HIV-positive patients].

Since the introduction of more effective antiretroviral therapy in HIV treatment, an increase in survival and in the quality of patients' life has been observed, due to the dramatic reduction in commonly occurring opportunistic diseases. The appearance of new clinical cases has, however, been observed, previously unrecorded probably due to the quicker negative evolution of AIDS. Pathologies such as lypodistrophy, cardiomyopathy, immune disease, are extremely widespread and partly linked to the natural history of HIV infections, and partly to the side effects of the treatments. Among such diseases, femoral head necrosis seems to occur fairly frequently and is characterised by a quick evolution. The emergence of coxalgia in HIV patients requires an early diagnosis through NMR or bone scan. Given the usual evolution of this pathology and the problems related to antiviral treatment, conservative treatment seems to have little possibility of success. A surgical replacement becomes essential in cases of invalidating necrosis, but there are still unresolved questions as regards risks of infection, bone integration, as well as local and systemic reactions to the prosthetic debris.

Adult↗
PubMed1999

Sequence evolution of the CCR5 chemokine receptor gene in primates.

The chemokine receptor CCR5 can serve as a coreceptor for M-tropic HIV-1 infection and both M-tropic and T-tropic SIV infection. We sequenced the entire CCR5 gene from 10 nonhuman primates: Pongo pygmaeus, Hylobates leucogenys, Trachypithecus francoisi, Trachypithecus phayrei, Pygathrix nemaeus, Rhinopithecus roxellanae, Rhinopithecus bieti, Rhinopithecus avunculus, Macaca assamensis, and Macaca arctoides. When compared with CCR5 sequences from humans and other primates, our results demonstrate that: (1) nucleotide and amino acid sequences of CCR5 among primates are highly homologous, with variations slightly concentrated on the amino and carboxyl termini; and (2) site Asp13, which is critical for CD4-independent binding of SIV gp120 to Macaca mulatta CCR5, was also present in all other nonhuman primates tested here, suggesting that those nonhuman primate CCR5s might also bind SIV gp120 without the presence of CD4. The topologies of CCR5 gene trees constructed here conflict with the putative opinion that the snub-nosed langurs compose a monophyletic group, suggesting that the CCR5 gene may not be a good genetic marker for low-level phylogenetic analysis. The evolutionary rate of CCR5 was calculated, and our results suggest a slowdown in primates after they diverged from rodents. The synonymous mutation rate of CCR5 in primates is constant, about 1.1 x 10(-9) synonymous mutations per site per year. Comparisons of Ka and Ks suggest that the CCR5 genes have undergone negative or purifying selection. Ka/Ks ratios from cercopithecines and colobines are significantly different, implying that selective pressures have played different roles in the two lineages.

Animals↗
PubMed2006

Effects of monotherapy with (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) on the evolution of a primary Simian immunodeficiency virus (SIV) isolate.

Determining the impact of antiretroviral therapy on virus evolution could advance the development of improved therapeutics/vaccines against HIV. Toward this goal, we analyzed virus burden, quasispecies complexity, and T cell responses in SIV/DeltaB670-infected rhesus macaques+/-treatment for 7 months with PMPA (2-30 weeks postinfection). Treatment divided the animals into two groups: poor responders (a reduction of < or =1 log) and responders (> or =2 log reduction) in virus burden. Virus evolution in poor responders and untreated controls was characterized by expression of a complex quasispecies that evolved as the disease progressed. This included the universal loss of a viral genotype selected against by in vitro passage in monkey cells and selected for by propagation in human cells. In contrast, a good response to PMPA was characterized by infection with a less complex quasispecies that evolved more slowly. Interestingly, in 2 of the best responders, the human-preferred genotype persisted until the study was discontinued (89 weeks p.i.). Neither virus burden nor the magnitude of the T cell response at 2 weeks postinfection predicted PMPA responsiveness. However, responders expressed a less complex quasispecies than nonresponders prior to treatment. These data suggest a role for intrinsic host factors in treatment responsiveness, and lend support for therapeutic vaccination as an adjunct to effective therapy.

Adenine↗
PubMed2001

Molecular characterization of a highly divergent HIV type 1 isolate obtained early in the AIDS epidemic from the Democratic Republic of Congo.

Numerous complete human immunodeficiency virus type 1 (HIV-1) genomes have been characterized for contemporary viruses, but few isolates obtained early in the HIV-1 epidemic have been studied. In this article, we describe the molecular characterization of an HIV-1 isolate (83CD003) that was obtained from an AIDS patient in Kinshasa, Democratic Republic of Congo (DRC) in 1983. The complete 83CD003 genome was sequenced in its entirety and found to encode uninterrupted open reading frames for all viral genes. Phylogenetic analysis revealed 83CD003 was a member of the major (M) group of HIV -1, but did not group with any of the known subtypes. Rather, it formed an independent lineage in all regions of its genome that was roughly equidistant from representatives of all other subtypes. Similarly, 83CD003 also did not cluster with any of several unclassified group M sequences that have been reported more recently to circulate in the DRC, suggesting that it may represent an early group M lineage thai is either rare or has gone extinct. The molecular clone of 83CD003 yielded an infectious virus after transfection into mammalian cells and its biological properties can be further studied.

Cell Line↗
PubMed1999

Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts.

Cyclosporine A therapy for prophylaxis against graft rejection revolutionized human organ transplantation. The immunosuppressant drugs cyclosporin A (CsA), FK506 and rapamycin block T-cell activation by interfering with the signal transduction pathway. The target proteins for CsA and FK506 were found to be cyclophilins and FK506-binding proteins, (FKBPs), respectively. They are unrelated in primary sequence, although both are peptidyl-prolyl cis-trans isomerases catalyzing the interconversion of peptidylprolyl imide bonds in peptide and protein substrates. However, the prolyl isomerase activity of these proteins is not essential for their immunosuppressive effects. Instead, the specific surfaces of the cyclophilin-CsA and FKBP-FK506 complexes mediate the immunosuppressive action. Moreover, the natural cellular functions of all but a few remain elusive. In some cases it could be demonstrated that prolyl isomerization is the rate-limiting step in protein folding in vitro, but many knockout mutants of single and multiple prolyl isomerases were viable with no detectable phenotype. Even though a direct requirement for in vivo protein folding could not be demonstrated, some important natural substrates of the prolyl isomerases are now known, and they demonstrate the great variety of prolyl isomerization functions in the living cell: (i) A human cyclophilin binds to the Gag polyprotein of the human immunodeficiency virus-1 (HIV-1) virion and was found to be essential for infection with HIV to occur, probably by removal of the virion coat. (ii) Together with heat shock protein (HSP) 90, a member of the chaperone family, high molecular weight cyclophilins and FKBPs bind and activate steroid receptors. This example also demonstrates that prolyl isomerases act together with other folding enzymes, for example the chaperones, and protein disulfide isomerases. (iii) An FKBP was found to act as a modulator of an intracellular calcium release channel. (iv) Along with the cyclophilins and FKBPs, a third class of prolyl isomerases exist, the parvulins. The human parvulin homologue Pin1 is a mitotic regulator essential for the G2/M transition of the eukaryotic cell cycle. These findings place proline isomerases at the intersection of protein folding, signal transduction, trafficking, assembly and cell cycle regulation.

Bacterial Proteins↗
PubMed2000

Virus and target cell evolution in human immunodeficiency virus type 1 infection.

Human immunodeficiency virus (HIV) infection leads to a prolonged struggle between a rapidly evolving viral population and a potent immune response. In the vast majority of infected individuals, the virus wins this struggle. In my laboratory, we focus on understanding both the viral and immune factors that contribute to this outcome. The results of our studies and those of many others indicate that HIV can escape a potent immune response by a combination of mechanisms including rapid mutation, shedding of decoy antigens, modulation of host major histocompatibility complex, and destruction of cytotoxic T lymphocytes. The target cells for viral infection change as the virus evolves to use different chemokine coreceptors for entry. The initial targets are activated and resting memory T cells that express both CD4 and CCR5, but both naive and memory CD4 T cells are targeted by viruses capable of using CXCR4 for entry, and macrophages become the primary target cells when most CD4 T cells are depleted. Compelling evidence is emerging that the availability of target cells for infection is as limiting for the spread of virus as the immune response.

HIV Infections↗
PubMed2006

[Hepatic steatosis: an emerging cause of cirrhosis in HIV patients].

Hepatic steatosis is an emerging cause of morbidity in antiretroviral therapy (ART)-experienced HIV patients. The influence of steatosis on fibrosis is poorly understood. We report two cases of rapid evolution of disseminated macrovacuolar steatofibrosis to cirrhosis. Both patients had no history of alcohol abuse, nor intravenous drug use and were tested negative for HCV (PCR RNA) and had no HBS antigen. Patient 1 had a past history of hypertrygliceridemia, but controlled with dietetic measures for 4 years prior to biopsy. The first hepatic biopsy showed a disseminated macrovacuolar steatosis (>80%). The patient had then cytolysis and an uncontrolled HIV viral load. The second biopsy was performed two years later, and HIV was controlled by a new line of ART. It showed a regression of the steatosis (10%) and a progression of the fibrosis with signs of cirrhosis. Patient 2 had a long history of HIV infection. He also had an uncontrolled dyslipidemia. The first biopsy was realised during a period of uncontrolled HIV infection and elevated liver enzymes. The biopsy showed a major macrovacuolar steatosis (>80%). The second biopsy was realised 6 years after and showed the same steatosis and signs of cirrhosis. The HIV infection was then under control. Observations reported here show a rapid evolution of liver steatosis to cirrhosis in HIV positive / HCV negative patients, despite the control of HIV infection. The implication of HAART remains unclear. In the era of HAART, liver steatosis can rapidly evoluate to cirrhosis without any risk factor except ART.

Adult↗
PubMed1997

Novel alleles of the chemokine-receptor gene CCR5.

The CCR5 gene encodes a cell-surface chemokine-receptor molecule that serves as a coreceptor for macrophage-tropic strains of HIV-1. Mutations in this gene may alter expression or function of the protein product, thereby altering chemokine binding/signaling or HIV-1 infection of cells that normally express CCR5 protein. Indeed, homozygotes for a 32-bp deletion allele of CCR5 (CCR5-delta 32), which causes a frameshift at amino acid 185, are relatively resistant to HIV-1 infection. Here we report the identification of 16 additional mutations in the coding region of the CCR5 gene, all but 3 of which are codon altering or "nonsynonymous." Most mutations were rare (found only once or twice in the sample); five were detected exclusively among African Americans, whereas eight were observed only in Caucasians. The mutations included 11 codon-altering nonsynonymous variants, one trinucleotide deletion, one chain-termination mutant, and three synonymous mutations. The high predominance of codon-altering alleles among CCR5 mutants (14/17 [81%], including CCR5-delta 32) is consistent with an adaptive accumulation of function-altering alleles for this gene, perhaps as a consequence of historic selective pressures.

Alleles↗
PubMed2000

Origins and evolution of AIDS viruses: estimating the time-scale.

The primate lentiviruses comprise SIV strains from various host species, as well as two viruses, HIV-1 and HIV-2, that cause AIDS in humans. The origins of HIV-1 and HIV-2 have been traced to cross-species transmissions from chimpanzees and sooty mangabey monkeys respectively. Two approaches have been taken to estimate the time-scale of the evolution of these viruses. Certain groups of SIV strains appear to have evolved in a host-dependent manner, implying a time-scale of many thousands or even millions of years. In stark contrast, molecular clock calculations have previously been used to estimate a time-scale of only tens or hundreds of years. Those calculations largely ignored heterogeneity of evolutionary rates across different sites within sequences. In fact, the distribution of rates at different sites seems extremely skewed in HIV-1, and so the time-depth of the primate lentivirus evolutionary tree may have been underestimated by at least a factor of ten. However, these date estimates still seem to be far too recent to be consistent with host-dependent evolution.

Animals↗