This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mothé, B. R.
Right arrow Articles by Watkins, D. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mothé, B. R.
Right arrow Articles by Watkins, D. I.

 Previous Article  |  Next Article 

Journal of Virology, February 2003, p. 2736-2740, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2736-2740.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Expression of the Major Histocompatibility Complex Class I Molecule Mamu-A*01 Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 Replication

Bianca R. Mothé,1,2 Jason Weinfurter,1 Chenxi Wang,3 William Rehrauer,1 Nancy Wilson,1 Todd M. Allen,1 David B. Allison,3 and David I. Watkins1,2*

Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715,1 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53792,2 Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 352943

Received 18 July 2002/ Accepted 7 November 2002


arrow
ABSTRACT
 
Several HLA alleles are associated with attenuated human immunodeficiency virus disease progression. We explored the relationship between the expression of particular major histocompatibility complex (MHC) class I alleles and viremia in simian immunodeficiency virus SIVmac239-infected macaques. Of the common MHC class I alleles, animals that expressed Mamu-A*01 exhibited the best control of viral replication.


arrow
TEXT
 
It is becoming increasingly clear that an individual's HLA genes can affect the outcome of human immunodeficiency virus (HIV) infection. Carrington et al. demonstrated that HLA-B*35 and -Cw*04 are present at a high frequency in individuals who progress rapidly to AIDS (5). Conversely, there is a heterozygous advantage in HIV infection (5). Furthermore, two specific alleles, HLA-B*57 and HLA-B*27, are associated with slow progression to disease (10, 12, 15). HLA-B*57-positive individuals develop a broad repertoire of cytotoxic T-lymphocyte (CTL) responses, especially against the Gag protein (15). HLA-B*27 binds an immunodominant epitope, KK10, derived from the Gag protein. In some patients, this response has selected for viral escape variants associated with progression to disease (8, 9).

Unique properties of the simian immunodeficiency virus (SIV)-infected rhesus macaque make it an ideal model for HIV infection (11). Both SIV and HIV-1 are primate lentiviruses, sharing similar genomic organizations, biological properties, and tissue tropisms (11). Both viruses use the CD4 molecule as the primary receptor and chemokine receptors as coreceptors (6). Persistent disease is the result of infection with HIV and SIV. Individuals experience ongoing viral replication, and set point viremia represents the equilibrium between the ability of the virus to replicate and the ability of the host's immune responses to limit replication. Virus replication is held in check for an extended period of time (usually years for humans), until viremia increases followed by the onset of AIDS (21). The concentration of viral RNA (vRNA) at the set point in plasma has been inversely correlated with progression to disease (14). Rhesus macaques infected with SIVmac239 develop symptoms characteristic of human AIDS, including depletion of CD4+ T cells followed by development of opportunistic infections.

We wanted to determine whether a major histocompatibility complex (MHC) effect existed in a cohort of animals experimentally infected with the molecular clone SIVmac239. Previous studies have shown that SIVmac251-infected animals that express the class I Mamu-A*01 molecule (18) control viremia more effectively than Mamu-A*01-negative animals. We therefore wanted to explore the role of Mamu-A*01 in controlling replication of SIVmac239.

To determine the effect of different MHC class I alleles on viral replication, we screened for the expression of the following eight common MHC class I alleles in our cohort of 53 SIVmac239-infected animals by PCR-sequence-specific primers (SSP): Mamu-A*01, Mamu-A*02, Mamu-A*08, Mamu-A*11, Mamu-B*01, Mamu-B*03, Mamu-B*04, and Mamu-B*17 (Table 1). These alleles were chosen because they purportedly bind SIV-derived epitopes (3, 4, 7). The 3'-terminal region of PCR-SSP primers targeted a nucleotide polymorphism unique to these eight Indian rhesus MHC class I alleles. Approximately 75 ng of genomic DNA was isolated from 200 µl of EDTA-anticoagulated whole blood or buffy coat for each sample in a total reaction volume of 25 µl. Final reaction mixtures contained 1x PCR buffer (Invitrogen, Carlsbad, Calif.) composed of 60 mM Tris-HCl (pH 9.5), 2 mM MgCl2, 15 mM ammonium sulfate, 410 µM each deoxynucleoside triphosphate (dNTP; Promega, Madison, Wis.), 0.5 µM each PCR-SSP primer, 0.3 µM each internal control primer, and 0.961 U of Platinum Taq polymerase (Gibco BRL, Life Technologies, Gaithersburg, Md.). The thermal cycling conditions were as follows: an initial 1 min of denaturation at 96°C, followed by 5 cycles of 96°C denaturation for 25 s, 70°C annealing for 50 s, and a 45-s extension at 72°C; and, finally, 4 cycles of 96°C denaturation for 25 s, 55°C annealing for 60 s, and a 120-s extension at 72°C. Subsequently, PCR products were electrophoresed on 2% agarose gels (0.5x Tris-borate-EDTA [TBE]) at a constant voltage and analyzed for the presence of the required internal control product and each of the specific allele amplicons relative to a 100-bp DNA ladder (Gibco BRL).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Viruses used, MHC class I alleles, set point viremia, and vaccination information for each SIV-infected animal in our cohorta

All macaques were infected with a molecularly cloned virus, SIVmac239 (Table 1). Three sets of viruses were used: SIVmac239/nef open and SIVmac239/nef stop, which were both expanded on rhesus peripheral blood lymphocytes (PBLs); and SIVmac239/nef open, which was expanded on CEMx174 cells only. SIVmac239/nef stop differs from SIVmac239/nef open by a stop codon present in the nef gene (13, 19). There is selection for full-length Nef protein in vivo, and the Nef open reading frame is restored within a few weeks after infection. The third virus stock was expanded in vitro on CEMx174 cells rather than on rhesus PBLs. Animals were infected intrarectally with SIVmac239/nef open (3,000 50% tissue culture infectious doses [TCID50]) and SIVmac239/nef stop (1,000 TCID50). Animals infected with SIVmac239/nef open expanded on CEMx174 cells only received 20 ng of p27 SIVmac239 intrarectally. A subset of animals was vaccinated according to DNA-modified vaccinia virus ankara (MVA) regimens containing different constructs (Table 1).

We stratified the animals based on their set point viremia. Viral loads were quantitated with the SIV branched DNA assay (Chiron Diagnostics, Emeryville, Calif.) and the Taqman kinetic reverse transcription (RT)-PCR assay. Plasma SIV RNA concentrations were measured every week for the first 4 weeks and then biweekly thereafter. Viral set points were measured between weeks 12 and 16, when plasma vRNA concentrations were constant for at least 2 weeks.

Viral load differences between groups of animals infected with SIVmac239 were tested for statistical significance with t tests after log transforming the data to improve normality and homoscedasticity. (Animal 83108 was not included in the analysis, because this animal was euthanized 5 weeks postinfection due to non-AIDS-related complications. No set point viremia was therefore available for this animal.) In addition, Levene's test for homoscedasticity was conducted, and if a difference was found to be significant, the Welch correction for unequal variances was employed. Finally, to further examine the robustness of the results, a nonparametric test, the Mann-Whitney U test, was performed. The P values for the nonparametric tests were calculated by exact methods. All P values are two tailed.

We found that the majority of animals with the lowest set point vRNA levels expressed Mamu-A*01. Between weeks 12 and 28 postinfection, Mamu-A*01-positive animals controlled viral replication more effectively than Mamu-A*01-negative animals (P = 0.001; t test) (Fig. 1). To ensure that the Mamu-A*01 effect is not due to a subset of vaccinated Mamu-A*01-positive animals, we removed these animals from the analysis. Indeed, vaccine-naive Mamu-A*01-positive animals restricted viral replication more efficiently than vaccine-naive Mamu-A*01-negative animals (P = 0.014; t test) (Fig. 2). We compared the virus loads between vaccinated and nonvaccinated Mamu-A*01-positive animals. We did not find a significant difference in set point viremia between these groups by either independent t test (P = 0.58) or Mann-Whitney test (P = 0.43). In addition to viral load analysis, we performed survival analysis by Cox regression (proportional hazards model) with A*01 status as a covariate. The hazard ratio of Mamu-A*01-positive animals to Mamu-A*01-negative animals is 0.76, which is not significant (P = 0.43). Nevertheless, analysis of survivorship as a function of vRNA revealed that survivorship is significantly inversely related to set point viremia (P < 0.001; Cox proportional hazards regression).



View larger version (16K):
[in this window]
[in a new window]
  		FIG. 1. Average plasma SIVmac239 vRNA concentration for all Mamu-A*01-positive animals versus Mamu-A*01-negative animals. The average plasma vRNA concentration for each of the two groups of animals is shown for the first 28 weeks postinfection. Mamu-A*01-positive animals significantly control viral replication more effectively than Mamu-A*01-negative animals (P = 0.001).



View larger version (17K):
[in this window]
[in a new window]
  		FIG. 2. Average plasma SIVmac239 vRNA concentration for control Mamu-A*01-positive animals versus Mamu-A*01-negative animals. The average plasma vRNA concentration for each of the two groups of animals is shown for the first 28 weeks postinfection. Control Mamu-A*01-positive animals significantly control viral replication more effectively than Mamu-A*01-negative animals (P = 0.014).

We have previously shown that Mamu-A*01-restricted epitopes dominate the anti-SIV CTL responses in Mamu-A*01-positive animals early in infection (16). Additionally, we have identified 14 different Mamu-A*01-restricted CTL epitopes, indicating that this MHC class I molecule engenders a broad repertoire of CTL responses (1). This may partially explain why Mamu-A*01-positive animals control viral replication more successfully than Mamu-A*01-negative animals. Furthermore, one of these responses, directed against the Tat28-35SL8 epitope, exerts selective pressure on the virus, as evidenced by viral escape from this response early in infection (2). This epitope has also been shown to be recognized by CTL with high functional avidity, requiring a low peptide concentration to trigger a CTL response (17).

The association of Mamu-A*01 with enhanced control of viral replication has been shown for infection with the heterogeneous biological isolate SIVmac251 (18), but not for infection with SHIV 89.6p. Our studies extend those findings to SIVmac239 replication. SHIV 89.6 is a chimeric virus created by using Env, as well as Tat, Vpu, and Rev from the HIV 89.6 isolate with the backbone of the molecular clone SIVmac239 (20). Mamu-A*01-restricted responses directed against SIV Env, Tat, Vpr, and Rev may therefore be partially responsible for the Mamu-A*01 effect in both SIVmac239 infection, shown here, and SIVmac251 infection (18). Tat28-35SL8 and other Mamu-A*01-restricted responses (1) may contribute to the effect of diminishing viral replication in Mamu-A*01-positive animals. Understanding how particular MHC genes affect viremia may provide insight into the correlates of protection from lentiviral infection.


arrow
ACKNOWLEDGMENTS
 
We thank Millie Schultz, Elizabeth Meek, and Christopher Fischer for technical help, in addition to Kevin Kunstman and Steve Wolinsky for plasma vRNA concentration analysis. We also thank Jody Helgeland for assistance with blood processing, Jacque Mitchen for coordinating all animal procedures, and Carol L. Emerson for performing all animal procedures.

This work was supported by NIH grants RR1537, AI46366, AI45461, and RR00167 (awarded to David I. Watkins). David I. Watkins is a recipient of an Elizabeth Glaser Scientist Award.


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Wisconsin Regional Primate Research Center, 1220 Capitol Ct., Madison, WI 53715-1299. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu. Back


arrow
REFERENCES
 
    1
  1. Allen, T. M., B. R. Mothe, J. Sidney, P. Jing, J. L. Dzuris, M. E. Liebl, T. U. Vogel, D. H. O'Connor, X. Wang, M. C. Wussow, J. A. Thomson, J. D. Altman, D. I. Watkins, and A. Sette. 2001. CD8+ lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule Mamu-A*01: implications for vaccine design and testing. J. Virol. 75:738-749.[Abstract/Free Full Text]
    2. 2
  2. Allen, T. M., D. H. O'Connor, P. Jing, J. L. Dzuris, B. R. Mothe, T. U. Vogel, E. Dunphy, M. E. Liebl, C. Emerson, N. Wilson, K. J. Kunstman, X. Wang, D. B. Allison, A. L. Hughes, R. C. Desrosiers, J. D. Altman, S. M. Wolinsky, A. Sette, and D. I. Watkins. 2000. Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature 407:386-390.[CrossRef][Medline]
    3. 3
  3. Allen, T. M., J. Sidney, M. F. del Guercio, R. L. Glickman, G. L. Lensmeyer, D. A. Wiebe, R. DeMars, C. D. Pauza, R. P. Johnson, A. Sette, and D. I. Watkins. 1998. Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus. J. Immunol. 160:6062-6071.[Abstract/Free Full Text]
    4. 4
  4. Allen, T. M., and D. I. Watkins. 1999. SIV and SHIV CTL epitopes identified in macaques, p. IV-45-IV-54. In B. T. Korber, C. Brander, B. F. Haynes, R. A. Koup, C. L. Kuiken, J. P. Moore, B. D. Walker, and D. I. Watkins (ed.), HIV Molecular Immunology Database. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, N.Mex.
    5. 5
  5. Carrington, M., G. W. Nelson, M. P. Martin, T. Kissner, D. Vlahov, J. J. Goedert, R. Kaslow, S. Buchbinder, K. Hoots, and S. J. O'Brien. 1999. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283:1748-1752.[Abstract/Free Full Text]
    6. 6
  6. Chen, Z., A. Gettie, D. D. Ho, and P. A. Marx. 1998. Primary SIVsm isolates use the CCR5 coreceptor from sooty mangabeys naturally infected in west Africa: a comparison of coreceptor usage of primary SIVsm, HIV-2, and SIVmac. Virology 246:113-124.[CrossRef][Medline]
    7. 7
  7. Evans, D. T., D. H. O'Connor, P. Jing, J. L. Dzuris, J. Sidney, J. da Silva, T. M. Allen, H. Horton, J. E. Venham, R. A. Rudersdorf, T. Vogel, C. D. Pauza, R. E. Bontrop, R. DeMars, A. Sette, A. L. Hughes, and D. I. Watkins. 1999. Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. Nat. Med. 5:1270-1276.[CrossRef][Medline]
    8. 8
  8. Goulder, P. J., M. A. Altfeld, E. S. Rosenberg, T. Nguyen, Y. Tang, R. L. Eldridge, M. M. Addo, S. He, J. S. Mukherjee, M. N. Phillips, M. Bunce, S. A. Kalams, R. P. Sekaly, B. D. Walker, and C. Brander. 2001. Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection. J. Exp. Med. 193:181-194.[Abstract/Free Full Text]
    9. 9
  9. Goulder, P. J., R. E. Phillips, R. A. Colbert, S. McAdam, G. Ogg, M. A. Nowak, P. Giangrande, G. Luzzi, B. Morgan, A. Edwards, A. J. McMichael, and S. Rowland-Jones. 1997. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat. Med. 3:212-217.[CrossRef][Medline]
    10. 10
  10. Hill, A. V. 1998. The immunogenetics of human infectious diseases. Annu. Rev. Immunol. 16:593-617.[CrossRef][Medline]
    11. 11
  11. Johnson, R. P. 1996. Macaque models for AIDS vaccine development. Curr. Opin. Immunol. 8:554-560.[CrossRef][Medline]
    12. 12
  12. Kaslow, R. A., M. Carrington, R. Apple, L. Park, A. Munoz, A. J. Saah, J. J. Goedert, C. Winkler, S. J. O'Brien, C. Rinaldo, R. Detels, W. Blattner, J. Phair, H. Erlich, and D. L. Mann. 1996. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat. Med. 2:405-411.[CrossRef][Medline]
    13. 13
  13. Lewis, M. G., S. Bellah, K. McKinnon, J. Yalley-Ogunro, P. M. Zack, W. R. Elkins, R. C. Desrosiers, and G. A. Eddy. 1994. Titration and characterization of two rhesus-derived SIVmac challenge stocks. AIDS Res. Hum. Retrovir. 10:213-220.[Medline]
    14. 14
  14. Mellors, J. W., C. R. Rinaldo, Jr., P. Gupta, R. M. White, J. A. Todd, and L. A. Kingsley. 1996. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272:1167-1170.[Abstract]
    15. 15
  15. Migueles, S. A., M. S. Sabbaghian, W. L. Shupert, M. P. Bettinotti, F. M. Marincola, L. Martino, C. W. Hallahan, S. M. Selig, D. Schwartz, J. Sullivan, and M. Connors. 2000. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc. Natl. Acad. Sci. USA 97:2709-2714.[Abstract/Free Full Text]
    16. 16
  16. Mothé, B. R., H. Horton, D. K. Carter, T. M. Allen, M. E. Liebl, P. Skinner, T. U. Vogel, S. Fuenger, K. Vielhuber, W. Rehrauer, N. Wilson, G. Franchini, J. D. Altman, A. Haase, L. J. Picker, D. B. Allison, and D. I. Watkins. 2002. Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection. J. Virol. 76:875-884.[Abstract/Free Full Text]
    17. 17
  17. O'Connor, D. H., T. M. Allen, T. U. Vogel, P. Jing, I. P. DeSouza, E. Dodds, E. J. Dunphy, C. Melsaether, B. Mothe, H. Yamamoto, H. Horton, N. Wilson, A. L. Hughes, and D. I. Watkins. 2002. Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection. Nat. Med. 8:493-499.[CrossRef][Medline]
    18. 18
  18. Pal, R., D. Venzon, N. L. Letvin, S. Santra, D. C. Montefiori, N. R. Miller, E. Tryniszewska, M. G. Lewis, T. C. VanCott, V. Hirsch, R. Woodward, A. Gibson, M. Grace, E. Dobratz, P. D. Markham, Z. Hel, J. Nacsa, M. Klein, J. Tartaglia, and G. Franchini. 2002. ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency. J. Virol. 76:292-302.[Abstract/Free Full Text]
    19. 19
  19. Regier, D. A., and R. C. Desrosiers. 1990. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res. Hum. Retrovir. 6:1221-1231.[Medline]
    20. 20
  20. Reimann, K. A., J. T. Li, R. Veazey, M. Halloran, I.-W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin. 1996. A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J. Virol. 70:6922-6928.[Abstract/Free Full Text]
    21. 21
  21. Sewell, A. K., D. A. Price, A. Oxenius, A. D. Kelleher, and R. E. Phillips. 2000. Cytotoxic T lymphocyte responses to human immunodeficiency virus: control and escape. Stem Cells 18:230-244.[CrossRef][Medline]

Journal of Virology, February 2003, p. 2736-2740, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2736-2740.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rosati, M., Bergamaschi, C., Valentin, A., Kulkarni, V., Jalah, R., Alicea, C., Patel, V., von Gegerfelt, A. S., Montefiori, D. C., Venzon, D. J., Khan, A. S., Draghia-Akli, R., Van Rompay, K. K. A., Felber, B. K., Pavlakis, G. N. (2009). DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge. Proc. Natl. Acad. Sci. USA 106: 15831-15836 [Abstract] [Full Text]  
  • Engram, J. C., Dunham, R. M., Makedonas, G., Vanderford, T. H., Sumpter, B., Klatt, N. R., Ratcliffe, S. J., Garg, S., Paiardini, M., McQuoid, M., Altman, J. D., Staprans, S. I., Betts, M. R., Garber, D. A., Feinberg, M. B., Silvestri, G. (2009). Vaccine-Induced, Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduce Virus Replication but Do Not Protect from Simian Immunodeficiency Virus Disease Progression. J. Immunol. 183: 706-717 [Abstract] [Full Text]  
  • Miura, T., Brumme, C. J., Brockman, M. A., Brumme, Z. L., Pereyra, F., Block, B. L., Trocha, A., John, M., Mallal, S., Harrigan, P. R., Walker, B. D. (2009). HLA-Associated Viral Mutations Are Common in Human Immunodeficiency Virus Type 1 Elite Controllers. J. Virol. 83: 3407-3412 [Abstract] [Full Text]  
  • Elbim, C., Monceaux, V., Mueller, Y. M., Lewis, M. G., Francois, S., Diop, O., Akarid, K., Hurtrel, B., Gougerot-Pocidalo, M.-A., Levy, Y., Katsikis, P. D., Estaquier, J. (2008). Early Divergence in Neutrophil Apoptosis between Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infections of Nonhuman Primates. J. Immunol. 181: 8613-8623 [Abstract] [Full Text]  
  • Demberg, T., Boyer, J. D., Malkevich, N., Patterson, L. J., Venzon, D., Summers, E. L., Kalisz, I., Kalyanaraman, V. S., Lee, E. M., Weiner, D. B., Robert-Guroff, M. (2008). Sequential Priming with Simian Immunodeficiency Virus (SIV) DNA Vaccines, with or without Encoded Cytokines, and a Replicating Adenovirus-SIV Recombinant Followed by Protein Boosting Does Not Control a Pathogenic SIVmac251 Mucosal Challenge. J. Virol. 82: 10911-10921 [Abstract] [Full Text]  
  • Schneidewind, A., Brockman, M. A., Sidney, J., Wang, Y. E., Chen, H., Suscovich, T. J., Li, B., Adam, R. I., Allgaier, R. L., Mothe, B. R., Kuntzen, T., Oniangue-Ndza, C., Trocha, A., Yu, X. G., Brander, C., Sette, A., Walker, B. D., Allen, T. M. (2008). Structural and Functional Constraints Limit Options for Cytotoxic T-Lymphocyte Escape in the Immunodominant HLA-B27-Restricted Epitope in Human Immunodeficiency Virus Type 1 Capsid. J. Virol. 82: 5594-5605 [Abstract] [Full Text]  
  • Mooij, P., Balla-Jhagjhoorsingh, S. S., Koopman, G., Beenhakker, N., van Haaften, P., Baak, I., Nieuwenhuis, I. G., Kondova, I., Wagner, R., Wolf, H., Gomez, C. E., Najera, J. L., Jimenez, V., Esteban, M., Heeney, J. L. (2008). Differential CD4+ versus CD8+ T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates. J. Virol. 82: 2975-2988 [Abstract] [Full Text]  
  • Mueller, Y. M., Do, D. H., Altork, S. R., Artlett, C. M., Gracely, E. J., Katsetos, C. D., Legido, A., Villinger, F., Altman, J. D., Brown, C. R., Lewis, M. G., Katsikis, P. D. (2008). IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses. J. Immunol. 180: 350-360 [Abstract] [Full Text]  
  • Schneidewind, A., Brockman, M. A., Yang, R., Adam, R. I., Li, B., Le Gall, S., Rinaldo, C. R., Craggs, S. L., Allgaier, R. L., Power, K. A., Kuntzen, T., Tung, C.-S., LaBute, M. X., Mueller, S. M., Harrer, T., McMichael, A. J., Goulder, P. J. R., Aiken, C., Brander, C., Kelleher, A. D., Allen, T. M. (2007). Escape from the Dominant HLA-B27-Restricted Cytotoxic T-Lymphocyte Response in Gag Is Associated with a Dramatic Reduction in Human Immunodeficiency Virus Type 1 Replication. J. Virol. 81: 12382-12393 [Abstract] [Full Text]  
  • Mueller, Y. M., Petrovas, C., Do, D. H., Altork, S. R., Fischer-Smith, T., Rappaport, J., Altman, J. D., Lewis, M. G., Katsikis, P. D. (2007). Early Establishment and Antigen Dependence of Simian Immunodeficiency Virus-Specific CD8+ T-Cell Defects. J. Virol. 81: 10861-10868 [Abstract] [Full Text]  
  • Loffredo, J. T., Maxwell, J., Qi, Y., Glidden, C. E., Borchardt, G. J., Soma, T., Bean, A. T., Beal, D. R., Wilson, N. A., Rehrauer, W. M., Lifson, J. D., Carrington, M., Watkins, D. I. (2007). Mamu-B*08-Positive Macaques Control Simian Immunodeficiency Virus Replication. J. Virol. 81: 8827-8832 [Abstract] [Full Text]  
  • von Gegerfelt, A. S., Rosati, M., Alicea, C., Valentin, A., Roth, P., Bear, J., Franchini, G., Albert, P. S., Bischofberger, N., Boyer, J. D., Weiner, D. B., Markham, P., Israel, Z. R., Eldridge, J. H., Pavlakis, G. N., Felber, B. K. (2007). Long-Lasting Decrease in Viremia in Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251 after Therapeutic DNA Immunization. J. Virol. 81: 1972-1979 [Abstract] [Full Text]  
  • Chung, C., Lee, W., Loffredo, J. T., Burwitz, B., Friedrich, T. C., Giraldo Vela, J. P., Napoe, G., Rakasz, E. G., Wilson, N. A., Allison, D. B., Watkins, D. I. (2007). Not All Cytokine-Producing CD8+ T Cells Suppress Simian Immunodeficiency Virus Replication. J. Virol. 81: 1517-1523 [Abstract] [Full Text]  
  • Chu, F., Lou, Z., Chen, Y. W., Liu, Y., Gao, B., Zong, L., Khan, A. H., Bell, J. I., Rao, Z., Gao, G. F. (2007). First Glimpse of the Peptide Presentation by Rhesus Macaque MHC Class I: Crystal Structures of Mamu-A*01 Complexed with Two Immunogenic SIV Epitopes and Insights into CTL Escape. J. Immunol. 178: 944-952 [Abstract] [Full Text]  
  • Yeh, W. W., Cale, E. M., Jaru-Ampornpan, P., Lord, C. I., Peyerl, F. W., Letvin, N. L. (2006). Compensatory substitutions restore normal core assembly in simian immunodeficiency virus isolates with gag epitope cytotoxic T-lymphocyte escape mutations.. J. Virol. 80: 8168-8177 [Abstract] [Full Text]  
  • Yant, L. J., Friedrich, T. C., Johnson, R. C., May, G. E., Maness, N. J., Enz, A. M., Lifson, J. D., O'Connor, D. H., Carrington, M., Watkins, D. I. (2006). The High-Frequency Major Histocompatibility Complex Class I Allele Mamu-B*17 Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 Replication.. J. Virol. 80: 5074-5077 [Abstract] [Full Text]  
  • Barratt-Boyes, S. M., Soloff, A. C., Gao, W., Nwanegbo, E., Liu, X., Rajakumar, P. A., Brown, K. N., Robbins, P. D., Murphey-Corb, M., Day, R. D., Gambotto, A. (2006). Broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors. J. Gen. Virol. 87: 139-149 [Abstract] [Full Text]  
  • Newberg, M. H., McEvers, K. J., Gorgone, D. A., Lifton, M. A., Baumeister, S. H. C., Veazey, R. S., Schmitz, J. E., Letvin, N. L. (2006). Immunodomination in the Evolution of Dominant Epitope-Specific CD8+ T Lymphocyte Responses in Simian Immunodeficiency Virus-Infected Rhesus Monkeys. J. Immunol. 176: 319-328 [Abstract] [Full Text]  
  • Casimiro, D. R., Wang, F., Schleif, W. A., Liang, X., Zhang, Z.-Q., Tobery, T. W., Davies, M.-E., McDermott, A. B., O'Connor, D. H., Fridman, A., Bagchi, A., Tussey, L. G., Bett, A. J., Finnefrock, A. C., Fu, T.-m., Tang, A., Wilson, K. A., Chen, M., Perry, H. C., Heidecker, G. J., Freed, D. C., Carella, A., Punt, K. S., Sykes, K. J., Huang, L., Ausensi, V. I., Bachinsky, M., Sadasivan-Nair, U., Watkins, D. I., Emini, E. A., Shiver, J. W. (2005). Attenuation of Simian Immunodeficiency Virus SIVmac239 Infection by Prophylactic Immunization with DNA and Recombinant Adenoviral Vaccine Vectors Expressing Gag. J. Virol. 79: 15547-15555 [Abstract] [Full Text]  
  • McDermott, A. B., O'Connor, D. H., Fuenger, S., Piaskowski, S., Martin, S., Loffredo, J., Reynolds, M., Reed, J., Furlott, J., Jacoby, T., Riek, C., Dodds, E., Krebs, K., Davies, M.-E., Schleif, W. A., Casimiro, D. R., Shiver, J. W., Watkins, D. I. (2005). Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques. J. Virol. 79: 15556-15566 [Abstract] [Full Text]  
  • Mao, H., Lafont, B. A. P., Igarashi, T., Nishimura, Y., Brown, C., Hirsch, V., Buckler-White, A., Sadjadpour, R., Martin, M. A. (2005). CD8+ and CD20+ Lymphocytes Cooperate To Control Acute Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimeric Virus Infections in Rhesus Monkeys: Modulation by Major Histocompatibility Complex Genotype. J. Virol. 79: 14887-14898 [Abstract] [Full Text]  
  • Krebs, K. C., Jin, Z., Rudersdorf, R., Hughes, A. L., O'Connor, D. H. (2005). Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques. J. Immunol. 175: 5230-5239 [Abstract] [Full Text]  
  • Liang, X., Casimiro, D. R., Schleif, W. A., Wang, F., Davies, M.-E., Zhang, Z.-Q., Fu, T.-M., Finnefrock, A. C., Handt, L., Citron, M. P., Heidecker, G., Tang, A., Chen, M., Wilson, K. A., Gabryelski, L., McElhaugh, M., Carella, A., Moyer, C., Huang, L., Vitelli, S., Patel, D., Lin, J., Emini, E. A., Shiver, J. W. (2005). Vectored Gag and Env but Not Tat Show Efficacy against Simian-Human Immunodeficiency Virus 89.6P Challenge in Mamu-A*01-Negative Rhesus Monkeys. J. Virol. 79: 12321-12331 [Abstract] [Full Text]  
  • Evans, D. T., Bricker, J. E., Sanford, H. B., Lang, S., Carville, A., Richardson, B. A., Piatak, M. Jr., Lifson, J. D., Mansfield, K. G., Desrosiers, R. C. (2005). Immunization of Macaques with Single-Cycle Simian Immunodeficiency Virus (SIV) Stimulates Diverse Virus-Specific Immune Responses and Reduces Viral Loads after Challenge with SIVmac239. J. Virol. 79: 7707-7720 [Abstract] [Full Text]  
  • Su, J., Luscher, M. A., Xiong, Y., Rustam, T., Amara, R. R., Rakasz, E., Robinson, H. L., MacDonald, K. S. (2005). Novel simian immunodeficiency virus CTL epitopes restricted by MHC class I molecule Mamu-B*01 are highly conserved for long term in DNA/MVA-vaccinated, SHIV-challenged rhesus macaques. Int Immunol 17: 637-648 [Abstract] [Full Text]  
  • Seaman, M. S., Santra, S., Newberg, M. H., Philippon, V., Manson, K., Xu, L., Gelman, R. S., Panicali, D., Mascola, J. R., Nabel, G. J., Letvin, N. L. (2005). Vaccine-Elicited Memory Cytotoxic T Lymphocytes Contribute to Mamu-A*01-Associated Control of Simian/Human Immunodeficiency Virus 89.6P Replication in Rhesus Monkeys. J. Virol. 79: 4580-4588 [Abstract] [Full Text]  
  • Sadagopal, S., Amara, R. R., Montefiori, D. C., Wyatt, L. S., Staprans, S. I., Kozyr, N. L., McClure, H. M., Moss, B., Robinson, H. L. (2005). Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2. J. Virol. 79: 3243-3253 [Abstract] [Full Text]  
  • Peyerl, F. W., Bazick, H. S., Newberg, M. H., Barouch, D. H., Sodroski, J., Letvin, N. L. (2004). Fitness Costs Limit Viral Escape from Cytotoxic T Lymphocytes at a Structurally Constrained Epitope. J. Virol. 78: 13901-13910 [Abstract] [Full Text]  
  • Loffredo, J. T., Sidney, J., Wojewoda, C., Dodds, E., Reynolds, M. R., Napoe, G., Mothe, B. R., O'Connor, D. H., Wilson, N. A., Watkins, D. I., Sette, A. (2004). Identification of Seventeen New Simian Immunodeficiency Virus-Derived CD8+ T Cell Epitopes Restricted by the High Frequency Molecule, Mamu-A*02, and Potential Escape from CTL Recognition. J. Immunol. 173: 5064-5076 [Abstract] [Full Text]  
  • Letvin, N. L., Huang, Y., Chakrabarti, B. K., Xu, L., Seaman, M. S., Beaudry, K., Korioth-Schmitz, B., Yu, F., Rohne, D., Martin, K. L., Miura, A., Kong, W.-P., Yang, Z.-Y., Gelman, R. S., Golubeva, O. G., Montefiori, D. C., Mascola, J. R., Nabel, G. J. (2004). Heterologous Envelope Immunogens Contribute to AIDS Vaccine Protection in Rhesus Monkeys. J. Virol. 78: 7490-7497 [Abstract] [Full Text]  
  • de Groot, N., Doxiadis, G. G., de Groot, N. G., Otting, N., Heijmans, C., Rouweler, A. J. M., Bontrop, R. E. (2004). Genetic Makeup of the DR Region in Rhesus Macaques: Gene Content, Transcripts, and Pseudogenes. J. Immunol. 172: 6152-6157 [Abstract] [Full Text]  
  • Mooij, P., Nieuwenhuis, I. G., Knoop, C. J., Doms, R. W., Bogers, W. M. J. M., ten Haaft, P. J. F., Niphuis, H., Koornstra, W., Bieler, K., Kostler, J., Morein, B., Cafaro, A., Ensoli, B., Wagner, R., Heeney, J. L. (2004). Qualitative T-Helper Responses to Multiple Viral Antigens Correlate with Vaccine-Induced Immunity to Simian/Human Immunodeficiency Virus Infection. J. Virol. 78: 3333-3342 [Abstract] [Full Text]  
  • McDermott, A. B., Mitchen, J., Piaskowski, S., De Souza, I., Yant, L. J., Stephany, J., Furlott, J., Watkins, D. I. (2004). Repeated Low-Dose Mucosal Simian Immunodeficiency Virus SIVmac239 Challenge Results in the Same Viral and Immunological Kinetics as High-Dose Challenge: a Model for the Evaluation of Vaccine Efficacy in Nonhuman Primates. J. Virol. 78: 3140-3144 [Abstract] [Full Text]  
  • Patterson, L. J., Malkevitch, N., Venzon, D., Pinczewski, J., Gomez-Roman, V. R., Wang, L., Kalyanaraman, V. S., Markham, P. D., Robey, F. A., Robert-Guroff, M. (2004). Protection against Mucosal Simian Immunodeficiency Virus SIVmac251 Challenge by Using Replicating Adenovirus-SIV Multigene Vaccine Priming and Subunit Boosting. J. Virol. 78: 2212-2221 [Abstract] [Full Text]  
  • O'Connor, D. H., Mothe, B. R., Weinfurter, J. T., Fuenger, S., Rehrauer, W. M., Jing, P., Rudersdorf, R. R., Liebl, M. E., Krebs, K., Vasquez, J., Dodds, E., Loffredo, J., Martin, S., McDermott, A. B., Allen, T. M., Wang, C., Doxiadis, G. G., Montefiori, D. C., Hughes, A., Burton, D. R., Allison, D. B., Wolinsky, S. M., Bontrop, R., Picker, L. J., Watkins, D. I. (2003). Major Histocompatibility Complex Class I Alleles Associated with Slow Simian Immunodeficiency Virus Disease Progression Bind Epitopes Recognized by Dominant Acute-Phase Cytotoxic-T-Lymphocyte Responses. J. Virol. 77: 9029-9040 [Abstract] [Full Text]  
  • Zhao, J., Pinczewski, J., Gomez-Roman, V. R., Venzon, D., Kalyanaraman, V. S., Markham, P. D., Aldrich, K., Moake, M., Montefiori, D. C., Lou, Y., Pavlakis, G. N., Robert-Guroff, M. (2003). Improved Protection of Rhesus Macaques against Intrarectal Simian Immunodeficiency Virus SIVmac251 Challenge by a Replication-Competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag Recombinant Priming/gp120 Boosting Regimen. J. Virol. 77: 8354-8365 [Abstract] [Full Text]  
  • Lafont, B. A. P., Buckler-White, A., Plishka, R., Buckler, C., Martin, M. A. (2003). Characterization of Pig-Tailed Macaque Classical MHC Class I Genes: Implications for MHC Evolution and Antigen Presentation in Macaques. J. Immunol. 171: 875-885 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mothé, B. R.
Right arrow Articles by Watkins, D. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mothé, B. R.
Right arrow Articles by Watkins, D. I.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»