Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection

@article{SalazarGonzalez2009GeneticIB,
  title={Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection},
  author={Jesus F. Salazar-Gonzalez and Maria G Salazar and Brandon F. Keele and Gerald H. Learn and Elena E. Giorgi and Hui Li and Julie M. Decker and Shuyi Wang and Joshua Baalwa and Matthias H. Kraus and Nicholas F. Parrish and Katharina S. Shaw and M. Brad Guffey and Katharine J. Bar and Katie L. Davis and Christina Ochsenbauer-Jambor and John C Kappes and Michael S. Saag and Myron S. Cohen and Joseph Mulenga and Cynthia A. Derdeyn and Susan A Allen and Eric Hunter and Martin Markowitz and Peter T. Hraber and Alan S. Perelson and Tanmoy Bhattacharya and Barton F. Haynes and Bette T. Korber and Beatrice H. Hahn and George M. Shaw},
  journal={The Journal of Experimental Medicine},
  year={2009},
  volume={206},
  pages={1273 - 1289}
}
Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and… 

Figures and Tables from this paper

Generation of Transmitted/Founder HIV-1 Infectious Molecular Clones and Characterization of Their Replication Capacity in CD4 T Lymphocytes and Monocyte-Derived Macrophages
TLDR
It is suggested that the acquisition of clinical HIV-1 subtype B infection occurs by mucosal exposure to virus that is not highly macrophage tropic and that the generation and initial biological characterization of 10 clade B T/F infectious molecular clones provides new opportunities to probe virus-host interactions involved in HIV- 1 transmission.
Rapid, complex adaptation of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression
TLDR
There was rapid virus adaptation following transmission, predominantly driven by CTL pressure, with most changes occurring during high viremia, which provides further challenges for vaccine protection.
Identification, Molecular Cloning, and Analysis of Full-Length Hepatitis C Virus Transmitted/Founder Genotypes 1, 3, and 4
TLDR
The identification of complete T/F genomes of HCV by single-genome sequencing of plasma viral RNA from acutely infected subjects shows that despite major differences in genome organization, replication strategy, and natural history, HCV (like HIV-1) diversifies essentially randomly early in infection, and as a consequence, sequences of actual T-F viruses can be identified.
Comparison of Viral Env Proteins from Acute and Chronic Infections with Subtype C Human Immunodeficiency Virus Type 1 Identifies Differences in Glycosylation and CCR5 Utilization and Suggests a New Strategy for Immunogen Design
TLDR
It is suggested that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.
Phenotypic properties of transmitted founder HIV-1
TLDR
TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance, which should be considered in the development and testing of AIDS vaccines.
Molecular Identification of Transmitted/Founder Hepatitis C Viruses and Their Progeny by Single Genome Sequencing.
TLDR
The methodological approach to SGS is described and it is shown how this strategy allows for the precise and unambiguous molecular identification of transmitted viruses as well as those that repopulate the body after drug or immune-mediated selective sweeps.
Genetic Identity and Biological Phenotype of a Transmitted/Founder Virus Representative of Nonpathogenic Simian Immunodeficiency Virus Infection in African Green Monkeys
TLDR
The T/F virus concept is extended to nonpathogenic SIV infections and provide an important new tool to define viral determinants of disease nonprogression.
Activities of Transmitted/Founder and Chronic Clade B HIV-1 Vpu and a C-Terminal Polymorphism Specifically Affecting Virion Release
TLDR
An amino acid near the C terminus of Vpu is identified that is specifically important for Vpu's ability to enhance the release of progeny virus from the host cell, supporting the notion of a new mechanism for this function of VPU.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 63 REFERENCES
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
TLDR
A mathematical model of random viral evolution and phylogenetic tree construction is developed and used to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection, suggesting a finite window of potential vulnerability of HIV- 1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing
TLDR
It is shown that HIV-1 env genes, other viral genes, and even full-length viral genomes responsible for productive clinical infection can be identified by SGA analysis of plasma virus sampled at intervals typical in large-scale vaccine trials and that pathways of viral diversification and immune escape can be determined accurately.
Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa
TLDR
Key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines are illustrated.
Human Immunodeficiency Virus Type 1 Population Genetics and Adaptation in Newly Infected Individuals
TLDR
The data indicate that acute subtype B HIV-1 infection usually results from transmission or outgrowth of single viral variants carrying mutations in CTL epitopes that were selected prior to transmission either in the donor or in a previous donor and that reversion of these mutations can be very slow.
Viral Sequence Evolution in Acute Hepatitis C Virus Infection
TLDR
The hypothesis that dysfunction of CD8+ T cells may be associated with failure to resolve HCV infections is supported and the rate of sequence evolution was observed to decline over the course of infection, possibly reflective of diminishing selection pressure by dysfunctional CD8-T cells.
The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection
TLDR
Kinetic analysis and mathematical modeling of virus immune escape showed that the contribution of CD8 T cell–mediated killing of productively infected cells was earlier and much greater than previously recognized and that it contributed to the initial decline of plasma virus in acute infection.
Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection
TLDR
The persistence of HIV sequences in peripheral blood mononuclear cells identical to those found at primary infection in the absence of continued virus expression provides an explanation for the previously observed differences in the composition of circulating DNA and RNA populations in sequential samples from seropositive individuals.
HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC
TLDR
This work investigates the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses or two closely related viruses, and highlights the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections.
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase
TLDR
In vivo mutation rates for HIV-1 are three and seven times higher than those previously reported for two other retroviruses, spleen necrosis virus and bovine leukemia virus, respectively, and the calculated in vivo mutation rate is about 20-fold lower than the error rate of purified HIV- 1 reverse transcriptase, with the same target sequence.
Antibody neutralization and escape by HIV-1
TLDR
The detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies is reported, indicating a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.
...
1
2
3
4
5
...