Dynamics of Envelope Evolution in Clade C SHIV-Infected Pig-Tailed Macaques during Disease Progression Analyzed by Ultra-Deep Pyrosequencing

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of non-human primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a non-progressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep pyrosequencing. Our results showed substantial envelope variations emerging in the progressor animal after the onset of AIDS. These envelope variations impacted the length of the variable loops and charges of different envelope regions. Additionally, multiple mutations were located at the CD4 and CCR5 binding sites, potentially affecting receptor binding affinity, viral fitness and they might be selected at late stages of disease. More importantly, these envelope mutations are not random since they had repeatedly been observed in a rhesus macaque and a human infant infected by either SHIV or HIV-1, respectively, carrying the parental envelope of the infectious molecular clone SHIV-1157ipd3N4. Moreover, similar mutations were also observed from other studies on different clades of envelopes regardless of the host species. These recurring mutations in different envelopes suggest that there may be a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression.

[1]  M. Nei,et al.  MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. , 2011, Molecular biology and evolution.

[2]  Xi Chen,et al.  Isolation of a Monoclonal Antibody That Targets the Alpha-2 Helix of gp120 and Represents the Initial Autologous Neutralizing-Antibody Response in an HIV-1 Subtype C-Infected Individual , 2011, Journal of Virology.

[3]  E. Bunnik,et al.  Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies , 2011, Journal of Virology.

[4]  J. Mascola,et al.  Antibody-Dependent Cell-Mediated Cytotoxicity in Simian Immunodeficiency Virus-Infected Rhesus Monkeys , 2011, Journal of Virology.

[5]  P. Ghys,et al.  Global trends in molecular epidemiology of HIV-1 during 2000–2007 , 2011, AIDS.

[6]  J. Overbaugh,et al.  Adaptation of Subtype A Human Immunodeficiency Virus Type 1 Envelope to Pig-Tailed Macaque Cells , 2011, Journal of Virology.

[7]  R. D’Aquila,et al.  Tenofovir (TDF)-selected or abacavir (ABC)-selected low-frequency HIV type 1 subpopulations during failure with persistent viremia as detected by ultradeep pyrosequencing. , 2011, AIDS research and human retroviruses.

[8]  Bette Korber,et al.  Epitope-Specific CD8+ T Lymphocytes Cross-Recognize Mutant Simian Immunodeficiency Virus (SIV) Sequences but Fail To Contain Very Early Evolution and Eventual Fixation of Epitope Escape Mutations during SIV Infection , 2011, Journal of Virology.

[9]  R. Arora,et al.  Vif Substitution Enables Persistent Infection of Pig-Tailed Macaques by Human Immunodeficiency Virus Type 1 , 2011, Journal of Virology.

[10]  Russell J. Davenport,et al.  Removing Noise From Pyrosequenced Amplicons , 2011, BMC Bioinformatics.

[11]  David L. Robertson,et al.  The Evolutionary Analysis of Emerging Low Frequency HIV-1 CXCR4 Using Variants through Time—An Ultra-Deep Approach , 2010, PLoS Comput. Biol..

[12]  G. Gottlieb,et al.  HIV-1 Envelope Subregion Length Variation during Disease Progression , 2010, PLoS pathogens.

[13]  J. Lundeberg,et al.  Dynamics of HIV-1 Quasispecies during Antiviral Treatment Dissected Using Ultra-Deep Pyrosequencing , 2010, PloS one.

[14]  Tommy F. Liu,et al.  Nucleic Acid Template and the Risk of a PCR-Induced HIV-1 Drug Resistance Mutation , 2010, PloS one.

[15]  W. Secor,et al.  Relative transmissibility of an R5 clade C simian-human immunodeficiency virus across different mucosae in macaques parallels the relative risks of sexual HIV-1 transmission in humans via different routes. , 2010, The Journal of infectious diseases.

[16]  J. Sodroski,et al.  A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer , 2010, Journal of Virology.

[17]  G. Vanham,et al.  HIV type 1 subtype A envelope genetic evolution in a slow progressing individual with consistent broadly neutralizing antibodies. , 2009, AIDS research and human retroviruses.

[18]  P. Lemey,et al.  A comparative study of HIV-1 clade C env evolution in a Zambian infant with an infected rhesus macaque during disease progression , 2009, AIDS (London).

[19]  C. Quince,et al.  Accurate determination of microbial diversity from 454 pyrosequencing data , 2009, Nature Methods.

[20]  Lynn Morris,et al.  Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection , 2009, PLoS pathogens.

[21]  R. Doms,et al.  Adaptive Mutations in a Human Immunodeficiency Virus Type 1 Envelope Protein with a Truncated V3 Loop Restore Function by Improving Interactions with CD4 , 2009, Journal of Virology.

[22]  Shiu-Lok Hu,et al.  Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus , 2009, Retrovirology.

[23]  Austin Hughes,et al.  Ultradeep Pyrosequencing Detects Complex Patterns of CD8+ T-Lymphocyte Escape in Simian Immunodeficiency Virus-Infected Macaques , 2009, Journal of Virology.

[24]  Ronald S Veazey,et al.  A macaque model of HIV-1 infection , 2009, Proceedings of the National Academy of Sciences.

[25]  Giovanni Chillemi,et al.  Massively parallel pyrosequencing highlights minority variants in the HIV-1 env quasispecies deriving from lymphomonocyte sub-populations , 2009, Retrovirology.

[26]  M. Humbert,et al.  SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys. , 2008, Retrovirology.

[27]  M. Churchill,et al.  Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net charge. , 2008, Virology.

[28]  Hanneke Schuitemaker,et al.  Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection , 2008, Journal of Virology.

[29]  L. Morris,et al.  The C3-V4 Region Is a Major Target of Autologous Neutralizing Antibodies in Human Immunodeficiency Virus Type 1 Subtype C Infection , 2007, Journal of Virology.

[30]  D. Church,et al.  Compartmentalization of the gut viral reservoir in HIV-1 infected patients , 2007, Retrovirology.

[31]  J. Hoxie,et al.  Effects of Partial Deletions within the Human Immunodeficiency Virus Type 1 V3 Loop on Coreceptor Tropism and Sensitivity to Entry Inhibitors , 2007, Journal of Virology.

[32]  Shiu-Lok Hu,et al.  Novel TRIM5 Isoforms Expressed by Macaca nemestrina , 2007, Journal of Virology.

[33]  Susan M. Huse,et al.  Accuracy and quality of massively parallel DNA pyrosequencing , 2007, Genome Biology.

[34]  M. Essex,et al.  Mutations in the V3 stem versus the V3 crown and C4 region have different effects on the binding and fusion steps of human immunodeficiency virus type 1 gp120 interaction with the CCR5 coreceptor. , 2007, Virology.

[35]  J. Overbaugh,et al.  Human Immunodeficiency Virus Type 1 V1-V2 Envelope Loop Sequences Expand and Add Glycosylation Sites over the Course of Infection, and These Modifications Affect Antibody Neutralization Sensitivity , 2006, Journal of Virology.

[36]  H. McClure,et al.  Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade C env , 2006, Journal of Virology.

[37]  Sang Joon Kim,et al.  A Mathematical Theory of Communication , 2006 .

[38]  Madhumita Mahalanabis,et al.  AminoTrack: Automating the Entry and Analysis of Mutations in Multiple Protein Sequences Using a Spreadsheet Format , 2006, BIOCOMP.

[39]  G. Ortí,et al.  Evolution of subtype C HIV-1 Env in a slowly progressing Zambian infant , 2005, Retrovirology.

[40]  Dorothy M. Lang,et al.  Selection for Human Immunodeficiency Virus Type 1 Envelope Glycosylation Variants with Shorter V1-V2 Loop Sequences Occurs during Transmission of Certain Genetic Subtypes and May Impact Viral RNA Levels , 2005, Journal of Virology.

[41]  C. Kankasa,et al.  Infectious Molecular Clone of a Recently Transmitted Pediatric Human Immunodeficiency Virus Clade C Isolate from Africa: Evidence of Intraclade Recombination , 2004, Journal of Virology.

[42]  A. Haase,et al.  Transmission, acute HIV-1 infection and the quest for strategies to prevent infection , 2003, Nature Medicine.

[43]  Martin A. Nowak,et al.  Antibody neutralization and escape by HIV-1 , 2003, Nature.

[44]  D. Montefiori,et al.  Molecular Evolution of Human Immunodeficiency Virus env in Humans and Monkeys: Similar Patterns Occur during Natural Disease Progression or Rapid Virus Passage , 2002, Journal of Virology.

[45]  D. Robertson,et al.  Near full-length clones and reference sequences for subtype C isolates of HIV type 1 from three different continents. , 2001, AIDS research and human retroviruses.

[46]  L. Chieco‐Bianchi,et al.  Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission , 2000, AIDS.

[47]  T. Gojobori,et al.  Reevaluation of Amino Acid Variability of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein and Prediction of New Discontinuous Epitopes , 2000, Journal of Virology.

[48]  S. Joag,et al.  A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has offered cytotropism. , 1997, Virology.

[49]  Ying Sun,et al.  The β-Chemokine Receptors CCR3 and CCR5 Facilitate Infection by Primary HIV-1 Isolates , 1996, Cell.

[50]  Stephen C. Peiper,et al.  Identification of a major co-receptor for primary isolates of HIV-1 , 1996, Nature.