DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients

Abstract

Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focusedmore » on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.« less

Authors:
 [1];  [2];  [3];  [2];  [1];  [2];  [1];  [1];  [1];  [3];  [4];  [5];  [6];  [4];  [6];  [7];  [5];  [3];  [1];  [1] more »;  [2];  [1];  [8] « less
  1. Emory Univ., Atlanta, GA (United States)
  2. Univ. of Oxford, Oxford (United Kingdom)
  3. Univ. of Alabama, Birmingham, AL (United States)
  4. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  5. International AIDS Vaccine Initiative, London (United Kingdom). Human Immunology Lab.
  6. Univ. of Pennsylvania, Philadelphia, PA (United States)
  7. Project San Francisco, Kigali (Rwanda). Rwanda-Zambia HIV Research Project
  8. Vaccine Research Center, Bethesda, MD (United States)
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1201431
Resource Type:
Accepted Manuscript
Journal Name:
PLoS Pathogens
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 1553-7374
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Yue, Ling, Pfafferott, Katja J., Baalwa, Joshua, Conrod, Karen, Dong, Catherine C., Chui, Cecilia, Rong, Rong, Claiborne, Daniel T., Prince, Jessica L., Tang, Jianming, Ribeiro, Ruy M., Cormier, Emmanuel, Hahn, Beatrice H., Perelson, Alan S., Shaw, George M., Karita, Etienne, Gilmour, Jill, Goepfert, Paul, Derdeyn, Cynthia A., Allen, Susan A., Borrow, Persephone, Hunter, Eric, and Douek, Daniel C.. Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. United States: N. p., 2015. Web. doi:10.1371/journal.ppat.1004565.
Yue, Ling, Pfafferott, Katja J., Baalwa, Joshua, Conrod, Karen, Dong, Catherine C., Chui, Cecilia, Rong, Rong, Claiborne, Daniel T., Prince, Jessica L., Tang, Jianming, Ribeiro, Ruy M., Cormier, Emmanuel, Hahn, Beatrice H., Perelson, Alan S., Shaw, George M., Karita, Etienne, Gilmour, Jill, Goepfert, Paul, Derdeyn, Cynthia A., Allen, Susan A., Borrow, Persephone, Hunter, Eric, & Douek, Daniel C.. Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients. United States. https://doi.org/10.1371/journal.ppat.1004565
Yue, Ling, Pfafferott, Katja J., Baalwa, Joshua, Conrod, Karen, Dong, Catherine C., Chui, Cecilia, Rong, Rong, Claiborne, Daniel T., Prince, Jessica L., Tang, Jianming, Ribeiro, Ruy M., Cormier, Emmanuel, Hahn, Beatrice H., Perelson, Alan S., Shaw, George M., Karita, Etienne, Gilmour, Jill, Goepfert, Paul, Derdeyn, Cynthia A., Allen, Susan A., Borrow, Persephone, Hunter, Eric, and Douek, Daniel C.. Thu . "Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients". United States. https://doi.org/10.1371/journal.ppat.1004565. https://www.osti.gov/servlets/purl/1201431.
@article{osti_1201431,
title = {Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients},
author = {Yue, Ling and Pfafferott, Katja J. and Baalwa, Joshua and Conrod, Karen and Dong, Catherine C. and Chui, Cecilia and Rong, Rong and Claiborne, Daniel T. and Prince, Jessica L. and Tang, Jianming and Ribeiro, Ruy M. and Cormier, Emmanuel and Hahn, Beatrice H. and Perelson, Alan S. and Shaw, George M. and Karita, Etienne and Gilmour, Jill and Goepfert, Paul and Derdeyn, Cynthia A. and Allen, Susan A. and Borrow, Persephone and Hunter, Eric and Douek, Daniel C.},
abstractNote = {Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.},
doi = {10.1371/journal.ppat.1004565},
journal = {PLoS Pathogens},
number = 1,
volume = 11,
place = {United States},
year = {Thu Jan 08 00:00:00 EST 2015},
month = {Thu Jan 08 00:00:00 EST 2015}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 39 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

HIV-1 Transmitting Couples Have Similar Viral Load Set-Points in Rakai, Uganda
journal, May 2010


The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection
journal, June 2009

  • Goonetilleke, Nilu; Liu, Michael K. P.; Salazar-Gonzalez, Jesus F.
  • The Journal of Experimental Medicine, Vol. 206, Issue 6
  • DOI: 10.1084/jem.20090365

Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers
journal, November 2008

  • Mahalanabis, Madhumita; Jayaraman, Pushpa; Miura, Toshiyuki
  • Journal of Virology, Vol. 83, Issue 2
  • DOI: 10.1128/JVI.01328-08

Escape from Autologous Neutralizing Antibodies in Acute/Early Subtype C HIV-1 Infection Requires Multiple Pathways
journal, September 2009


Long-term HIV-1 infection without immunologic progression
journal, January 1994


T Cell Immunity in Acute HIV‐1 Infection
journal, October 2010

  • Streeck, Hendrik; Nixon, Douglas F.
  • The Journal of Infectious Diseases, Vol. 202, Issue S2
  • DOI: 10.1086/655652

A Longitudinal Study of Neutralizing Antibodies and Disease Progression in HIV‐1–Infected Subjects
journal, June 1999

  • Cecilia, D.; Kleeberger, C.; Muñoz, A.
  • The Journal of Infectious Diseases, Vol. 179, Issue 6
  • DOI: 10.1086/314773

CD8+ T-cell responses to different HIV proteins have discordant associations with viral load
journal, December 2006

  • Kiepiela, Photini; Ngumbela, Kholiswa; Thobakgale, Christina
  • Nature Medicine, Vol. 13, Issue 1
  • DOI: 10.1038/nm1520

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
journal, June 2009

  • Salazar-Gonzalez, Jesus F.; Salazar, Maria G.; Keele, Brandon F.
  • The Journal of Experimental Medicine, Vol. 206, Issue 6
  • DOI: 10.1084/jem.20090378

Quantitation of HIV-1 RNA in Plasma Predicts Outcome after Seroconversion
journal, April 1995


HLA Allele Sharing and HIV Type 1 Viremia in Seroconverting Zambians with Known Transmitting Partners
journal, January 2004

  • Tang, Jianming; Tang, Shenghui; Lobashevsky, Elena
  • AIDS Research and Human Retroviruses, Vol. 20, Issue 1
  • DOI: 10.1089/088922204322749468

Chronic HIV infection affects the expression of the 2 transcription factors required for CD8 T-cell differentiation into cytolytic effectors
journal, May 2012


Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS
journal, February 1997

  • Goulder, Philip J. R.; Phillips, Rodney E.; Colbert, Robert A.
  • Nature Medicine, Vol. 3, Issue 2
  • DOI: 10.1038/nm0297-212

Natural History of Human Immunodeficiency Virus Type 1 Viremia after Seroconversion and Proximal to AIDS in a Large Cohort of Homosexual Men
journal, March 2000

  • Lyles, Robert H.; Muñoz, Alvaro; Yamashita, Traci E.
  • The Journal of Infectious Diseases, Vol. 181, Issue 3
  • DOI: 10.1086/315339

Influence of HLA-C Expression Level on HIV Control
journal, April 2013


Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
journal, May 2008

  • Keele, B. F.; Giorgi, E. E.; Salazar-Gonzalez, J. F.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 21
  • DOI: 10.1073/pnas.0802203105

Impact of HLA-B*81-Associated Mutations in HIV-1 Gag on Viral Replication Capacity
journal, January 2012

  • Wright, J. K.; Naidoo, V. L.; Brumme, Z. L.
  • Journal of Virology, Vol. 86, Issue 6
  • DOI: 10.1128/jvi.06682-11

CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes
journal, February 2003

  • Janssen, Edith M.; Lemmens, Edward E.; Wolfe, Tom
  • Nature, Vol. 421, Issue 6925
  • DOI: 10.1038/nature01441

Control of Viremia in Simian Immunodeficiency Virus Infection by CD8+ Lymphocytes
journal, February 1999


Elite Suppressor–Derived HIV-1 Envelope Glycoproteins Exhibit Reduced Entry Efficiency and Kinetics
journal, April 2009


HLA-A*7401–Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703
journal, April 2011

  • Matthews, Philippa C.; Adland, Emily; Listgarten, Jennifer
  • The Journal of Immunology, Vol. 186, Issue 10
  • DOI: 10.4049/jimmunol.1003711

Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection
journal, January 1998


The Antibody Response against HIV-1
journal, November 2011


Envelope-Constrained Neutralization-Sensitive HIV-1 After Heterosexual Transmission
journal, March 2004


Long-Term Survivors with HIV-1 Infection: Incubation Period and Longitudinal Patterns of CD4+ Lymphocytes
journal, January 1995

  • Muñoz, Alvaro; Kirby, Alison J.; He, yanhua D.
  • Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology, Vol. 8, Issue 5
  • DOI: 10.1097/00042560-199504120-00010

Elucidating the elite: mechanisms of control in HIV-1 infection
journal, December 2009

  • O’Connell, Karen A.; Bailey, Justin R.; Blankson, Joel N.
  • Trends in Pharmacological Sciences, Vol. 30, Issue 12
  • DOI: 10.1016/j.tips.2009.09.005

Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection
journal, January 2003


Rapid evolution of the neutralizing antibody response to HIV type 1 infection
journal, March 2003

  • Richman, D. D.; Wrin, T.; Little, S. J.
  • Proceedings of the National Academy of Sciences, Vol. 100, Issue 7
  • DOI: 10.1073/pnas.0630530100

Antibody neutralization and escape by HIV-1
journal, March 2003

  • Wei, Xiping; Decker, Julie M.; Wang, Shuyi
  • Nature, Vol. 422, Issue 6929
  • DOI: 10.1038/nature01470

Lytic Granule Loading of CD8+ T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control
journal, December 2008


Dramatic Rise in Plasma Viremia after CD8 + T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques
journal, March 1999

  • Jin, Xia; Bauer, Daniel E.; Tuttleton, Sarah E.
  • The Journal of Experimental Medicine, Vol. 189, Issue 6
  • DOI: 10.1084/jem.189.6.991

Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones
journal, February 2013


Genetic and Immunologic Heterogeneity among Persons Who Control HIV Infection in the Absence of Therapy
journal, February 2008

  • Pereyra, Florencia; Addo, Marylyn M.; Kaufmann, Daniel E.
  • The Journal of Infectious Diseases, Vol. 197, Issue 4
  • DOI: 10.1086/526786

Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV infection
journal, September 1997

  • Pantaleo, G.; Soudeyns, H.; Demarest, J. F.
  • Proceedings of the National Academy of Sciences, Vol. 94, Issue 18
  • DOI: 10.1073/pnas.94.18.9848

Impaired Replication Capacity of Acute/Early Viruses in Persons Who Become HIV Controllers
journal, May 2010

  • Miura, Toshiyuki; Brumme, Zabrina L.; Brockman, Mark A.
  • Journal of Virology, Vol. 84, Issue 15
  • DOI: 10.1128/jvi.00286-10

HIV and SIV CTL escape: implications for vaccine design
journal, August 2004

  • Goulder, Philip J. R.; Watkins, David I.
  • Nature Reviews Immunology, Vol. 4, Issue 8
  • DOI: 10.1038/nri1417

Kinetics of Expansion of Epitope-Specific T Cell Responses during Primary HIV-1 Infection
journal, May 2009

  • Turnbull, Emma L.; Wong, MaiLee; Wang, Shuyi
  • The Journal of Immunology, Vol. 182, Issue 11
  • DOI: 10.4049/jimmunol.0803658

The Natural History of HIV-1 Infection: Virus Load and Virus Phenotype Independent Determinants of Clinical Course?
journal, October 1994

  • Jurriaans, Suzanne; Van Gemen, Bob; Weverling, Gerrit Jan
  • Virology, Vol. 204, Issue 1
  • DOI: 10.1006/viro.1994.1526

Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients
journal, April 2008

  • Goepfert, Paul A.; Lumm, Wendy; Farmer, Paul
  • The Journal of Experimental Medicine, Vol. 205, Issue 5
  • DOI: 10.1084/jem.20072457

HIV evolution: CTL escape mutation and reversion after transmission
journal, February 2004

  • Leslie, A. J.; Pfafferott, K. J.; Chetty, P.
  • Nature Medicine, Vol. 10, Issue 3
  • DOI: 10.1038/nm992

Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans
journal, June 2012

  • McLaren, Paul J.; Ripke, Stephan; Pelak, Kimberly
  • Human Molecular Genetics, Vol. 21, Issue 19
  • DOI: 10.1093/hmg/dds226

Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage
journal, March 2008


Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load
journal, September 2010


Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1
journal, January 2009


The Rate of Immune Escape Vanishes When Multiple Immune Responses Control an HIV Infection
journal, August 2013

  • van Deutekom, Hanneke W. M.; Wijnker, Gilles; de Boer, Rob J.
  • The Journal of Immunology, Vol. 191, Issue 6
  • DOI: 10.4049/jimmunol.1300962

Impact of MHC class I diversity on immune control of immunodeficiency virus replication
journal, August 2008

  • Goulder, Philip J. R.; Watkins, David I.
  • Nature Reviews Immunology, Vol. 8, Issue 8
  • DOI: 10.1038/nri2357

Maintenance of viral suppression in HIV-1–infected HLA-B*57+ elite suppressors despite CTL escape mutations
journal, May 2006

  • Bailey, Justin R.; Williams, Thomas M.; Siliciano, Robert F.
  • Journal of Experimental Medicine, Vol. 203, Issue 5
  • DOI: 10.1084/jem.20052319

Elite control of HIV infection: implications for vaccine design
journal, November 2008


Phylogenetic Evaluation of Kenyan HIV Type 1 Isolates
journal, April 1997

  • Poss, Mary; Gosink, John; Thomas, Elaine
  • AIDS Research and Human Retroviruses, Vol. 13, Issue 6
  • DOI: 10.1089/aid.1997.13.493

Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape
journal, May 2012


Definition of the viral targets of protective HIV-1-specific T cell responses
journal, January 2011

  • Mothe, Beatriz; Llano, Anuska; Ibarrondo, Javier
  • Journal of Translational Medicine, Vol. 9, Issue 1
  • DOI: 10.1186/1479-5876-9-208

Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response
journal, November 2004

  • Jones, Nicola A.; Wei, Xiping; Flower, Darren R.
  • The Journal of Experimental Medicine, Vol. 200, Issue 10, p. 1243-1256
  • DOI: 10.1084/jem.20040511

Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703–positive individuals and their transmission recipients
journal, March 2009

  • Crawford, Hayley; Lumm, Wendy; Leslie, Alasdair
  • The Journal of Experimental Medicine, Vol. 206, Issue 4
  • DOI: 10.1084/jem.20081984

Additive Contribution of HLA Class I Alleles in the Immune Control of HIV-1 Infection
journal, July 2010

  • Leslie, Alasdair; Matthews, Philippa C.; Listgarten, Jennifer
  • Journal of Virology, Vol. 84, Issue 19
  • DOI: 10.1128/jvi.00320-10

Role of donor genital tract HIV-1 diversity in the transmission bottleneck
journal, November 2011

  • Boeras, D. I.; Hraber, P. T.; Hurlston, M.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 46
  • DOI: 10.1073/pnas.1103764108

Fitness Costs and Diversity of the Cytotoxic T Lymphocyte (CTL) Response Determine the Rate of CTL Escape during Acute and Chronic Phases of HIV Infection
journal, August 2011

  • Ganusov, V. V.; Goonetilleke, N.; Liu, M. K. P.
  • Journal of Virology, Vol. 85, Issue 20
  • DOI: 10.1128/JVI.00655-11

A Whole-Genome Association Study of Major Determinants for Host Control of HIV-1
journal, August 2007


Viral Replication Capacity as a Correlate of HLA B57/B5801-Associated Nonprogressive HIV-1 Infection
journal, August 2007


Clinical Outcomes of Elite Controllers, Viremic Controllers, and Long‐Term Nonprogressors in the US Department of Defense HIV Natural History Study
journal, December 2009

  • Okulicz, Jason F.; Marconi, Vincent C.; Landrum, Michael L.
  • The Journal of Infectious Diseases, Vol. 200, Issue 11
  • DOI: 10.1086/646609

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors
journal, December 2006

  • Blankson, Joel N.; Bailey, Justin R.; Thayil, Seema
  • Journal of Virology, Vol. 81, Issue 5
  • DOI: 10.1128/jvi.02165-06

HIV Controllers: A Homogeneous Group of HIV-1--Infected Patients with Spontaneous Control of Viral Replication
journal, October 2005

  • Lambotte, O.; Boufassa, F.; Madec, Y.
  • Clinical Infectious Diseases, Vol. 41, Issue 7
  • DOI: 10.1086/433188

Neutralizing and Infection-Enhancing Antibody Responses to Human Immunodeficiency Virus Type 1 in Long-Term Nonprogressors
journal, January 1996

  • Montefiori, David C.; Pantaleo, Giuseppe; Fink, Lisa M.
  • The Journal of Infectious Diseases, Vol. 173, Issue 1
  • DOI: 10.1093/infdis/173.1.60

Role of Transmitted Gag CTL Polymorphisms in Defining Replicative Capacity and Early HIV-1 Pathogenesis
journal, November 2012


The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels
journal, January 1993


Early Selection in Gag by Protective HLA Alleles Contributes to Reduced HIV-1 Replication Capacity That May Be Largely Compensated for in Chronic Infection
journal, September 2010

  • Brockman, Mark A.; Brumme, Zabrina L.; Brumme, Chanson J.
  • Journal of Virology, Vol. 84, Issue 22
  • DOI: 10.1128/jvi.01086-10

Large-scale amplification, cloning and sequencing of near full-length HIV-1 subtype C genomes
journal, September 2006


Common Genetic Variation and the Control of HIV-1 in Humans
journal, December 2009


Escape from CD8 + T Cell Responses in Mamu-B*00801 + Macaques Differentiates Progressors from Elite Controllers
journal, March 2012

  • Mudd, Philip A.; Ericsen, Adam J.; Burwitz, Benjamin J.
  • The Journal of Immunology, Vol. 188, Issue 7
  • DOI: 10.4049/jimmunol.1102470

HIV-1 replicative fitness in elite controllers
journal, January 2011


Cumulative Impact of Host and Viral Factors on HIV-1 Viral-Load Control during Early Infection
journal, October 2012

  • Yue, L.; Prentice, H. A.; Farmer, P.
  • Journal of Virology, Vol. 87, Issue 2
  • DOI: 10.1128/JVI.02118-12

Immune responses to HIV and SIV in mucosal tissues: ‘location, location, location’
journal, January 2010


HIV RNA level in early infection is predicted by viral load in the transmission source
journal, January 2010


Influence of Gag-Protease-Mediated Replication Capacity on Disease Progression in Individuals Recently Infected with HIV-1 Subtype C
journal, February 2011

  • Wright, J. K.; Novitsky, V.; Brockman, M. A.
  • Journal of Virology, Vol. 85, Issue 8
  • DOI: 10.1128/JVI.02520-10

Genetic Characterization of Human Immunodeficiency Virus Type 1 in Elite Controllers: Lack of Gross Genetic Defects or Common Amino Acid Changes
journal, June 2008

  • Miura, Toshiyuki; Brockman, Mark A.; Brumme, Chanson J.
  • Journal of Virology, Vol. 82, Issue 17
  • DOI: 10.1128/JVI.00535-08

HLA-Associated Alterations in Replication Capacity of Chimeric NL4-3 Viruses Carrying gag-protease from Elite Controllers of Human Immunodeficiency Virus Type 1
journal, October 2008

  • Miura, Toshiyuki; Brockman, Mark A.; Brumme, Zabrina L.
  • Journal of Virology, Vol. 83, Issue 1
  • DOI: 10.1128/JVI.01471-08

Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8+ T Cells
journal, August 2010

  • Payne, Rebecca P.; Kløverpris, Henrik; Sacha, Jonah B.
  • Journal of Virology, Vol. 84, Issue 20
  • DOI: 10.1128/JVI.00793-10

Sensitivity of Human Immunodeficiency Virus Type 1 to the Fusion Inhibitor T-20 Is Modulated by Coreceptor Specificity Defined by the V3 Loop of gp120
journal, September 2000


Emergence of Resistant Human Immunodeficiency Virus Type 1 in Patients Receiving Fusion Inhibitor (T-20) Monotherapy
journal, June 2002


Evidence for Persistent Low-Level Viremia in Individuals Who Control Human Immunodeficiency Virus in the Absence of Antiretroviral Therapy
journal, October 2008

  • Hatano, Hiroyu; Delwart, Eric L.; Norris, Philip J.
  • Journal of Virology, Vol. 83, Issue 1
  • DOI: 10.1128/JVI.01763-08

HIV-1 infection–induced apoptotic microparticles inhibit human DCs via CD44
journal, November 2012

  • Frleta, Davor; Ochoa, Carolyn E.; Kramer, Holger B.
  • Journal of Clinical Investigation, Vol. 122, Issue 12
  • DOI: 10.1172/JCI64439

Frequency and Phenotype of Human Immunodeficiency Virus Envelope-Specific B Cells from Patients with Broadly Cross-Neutralizing Antibodies
journal, October 2008

  • Doria-Rose, N. A.; Klein, R. M.; Manion, M. M.
  • Journal of Virology, Vol. 83, Issue 1
  • DOI: 10.1128/JVI.01583-08

Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers
journal, January 2009


Specificity of the autologous neutralizing antibody response
journal, January 2009


Clade-Specific Differences between Human Immunodeficiency Virus Type 1 Clades B and C: Diversity and Correlations in C3-V4 Regions of gp120
journal, May 2007

  • Gnanakaran, S.; Lang, Dorothy; Daniels, Marcus
  • Journal of Virology, Vol. 81, Issue 9
  • DOI: 10.1128/JVI.01954-06

The B Cell Response Is Redundant and Highly Focused on V1V2 during Early Subtype C Infection in a Zambian Seroconverter
journal, October 2010

  • Lynch, R. M.; Rong, R.; Boliar, S.
  • Journal of Virology, Vol. 85, Issue 2
  • DOI: 10.1128/JVI.02006-10

Molecular Epidemiology of Human Immunodeficiency Virus Type 1 Transmission in a Heterosexual Cohort of Discordant Couples in Zambia
journal, January 2002


Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
text, January 2009

  • S., Perelson, Alan; Christina, Ochsenbauer-Jambor,; C., Kappas, John
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/1n1a-3d64

Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
text, January 2009

  • Joseph, Mulenga,; G., Salazar, Maria; Susan, Allen,
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/gak8-9b11

The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection
text, January 2009

  • Nilu, Goonetilleke,; Persephone, Borrow,; Elena, Giorgi,
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/pft2-qa63

Virologic and Immunologic Characterization of Long-Term Survivors of Human Immunodeficiency Virus Type 1 Infection
book, January 1995

  • Cao, Yunzhen; Qin, Limo; Zhang, Linqi
  • Global Challenge of AIDS
  • DOI: 10.1159/000424936

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
text, January 2008

  • F., Salazar-Gonzalez, Jesus; P., Busch, Michael; S., Perelson, Alan
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/f6s9-vz03

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
text, January 2010

  • Libraries, The University of North Carolina at Chapel Hill University
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/gv0c-ds30

Phylogenetic Approach Reveals That Virus Genotype Largely Determines HIV Set-Point Viral Load
text, January 2010


Dramatic Rise in Plasma Viremia after CD8 + T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques
journal, March 1999

  • Jin, Xia; Bauer, Daniel E.; Tuttleton, Sarah E.
  • The Journal of Experimental Medicine, Vol. 189, Issue 6
  • DOI: 10.1084/jem.189.6.991

Determinants of Human Immunodeficiency Virus Type 1 Escape from the Primary CD8+ Cytotoxic T Lymphocyte Response
journal, November 2004

  • Jones, Nicola A.; Wei, Xiping; Flower, Darren R.
  • The Journal of Experimental Medicine, Vol. 200, Issue 10, p. 1243-1256
  • DOI: 10.1084/jem.20040511

Maintenance of viral suppression in HIV-1–infected HLA-B*57+ elite suppressors despite CTL escape mutations
journal, May 2006

  • Bailey, Justin R.; Williams, Thomas M.; Siliciano, Robert F.
  • Journal of Experimental Medicine, Vol. 203, Issue 5
  • DOI: 10.1084/jem.20052319

Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703–positive individuals and their transmission recipients
journal, March 2009

  • Crawford, Hayley; Lumm, Wendy; Leslie, Alasdair
  • The Journal of Experimental Medicine, Vol. 206, Issue 4
  • DOI: 10.1084/jem.20081984

The Rate of Immune Escape Vanishes When Multiple Immune Responses Control an HIV Infection
journal, August 2013

  • van Deutekom, Hanneke W. M.; Wijnker, Gilles; de Boer, Rob J.
  • The Journal of Immunology, Vol. 191, Issue 6
  • DOI: 10.4049/jimmunol.1300962

Works referencing / citing this record:

Alterations of HIV-1 envelope phenotype and antibody-mediated neutralization by signal peptide mutations
journal, January 2018


CD8+ T cells in HIV control, cure and prevention
journal, February 2020

  • Collins, David R.; Gaiha, Gaurav D.; Walker, Bruce D.
  • Nature Reviews Immunology, Vol. 20, Issue 8
  • DOI: 10.1038/s41577-020-0274-9

Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
journal, April 2018

  • Casado, Concepción; Marrero-Hernández, Sara; Márquez-Arce, Daniel
  • mBio, Vol. 9, Issue 2
  • DOI: 10.1128/mbio.02338-17

Role of HLA Adaptation in HIV Evolution
journal, January 2016

  • Kløverpris, Henrik N.; Leslie, Alasdair; Goulder, Philip
  • Frontiers in Immunology, Vol. 6
  • DOI: 10.3389/fimmu.2015.00665

Heterosexual Transmission of Subtype C HIV-1 Selects Consensus-Like Variants without Increased Replicative Capacity or Interferon-α Resistance
journal, September 2015


Success and failure of the cellular immune response against HIV-1
journal, May 2015

  • Migueles, Stephen A.; Connors, Mark
  • Nature Immunology, Vol. 16, Issue 6
  • DOI: 10.1038/ni.3161

Identification of Immunodominant HIV-1 Epitopes Presented by HLA-C*12:02, a Protective Allele, Using an Immunopeptidomics Approach
journal, June 2019

  • Chikata, Takayuki; Paes, Wayne; Akahoshi, Tomohiro
  • Journal of Virology, Vol. 93, Issue 17
  • DOI: 10.1128/jvi.00634-19

Resistance to type 1 interferons is a major determinant of HIV-1 transmission fitness
journal, January 2017

  • Iyer, Shilpa S.; Bibollet-Ruche, Frederic; Sherrill-Mix, Scott
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 4
  • DOI: 10.1073/pnas.1620144114

HIV control: Is getting there the same as staying there?
journal, November 2018


A Naturally Occurring rev1-vpu Fusion Gene Does Not Confer a Fitness Advantage to HIV-1
journal, November 2015


Alterations of HIV-1 envelope phenotype and antibody-mediated neutralization by signal peptide mutations
journal, January 2018


Composite Sequence–Structure Stability Models as Screening Tools for Identifying Vulnerable Targets for HIV Drug and Vaccine Development
journal, November 2015

  • Manocheewa, Siriphan; Mittler, John; Samudrala, Ram
  • Viruses, Vol. 7, Issue 11
  • DOI: 10.3390/v7112901