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Article ; Online: BLT humanized mice as a small animal model of HIV infection.

Karpel, Marshall E / Boutwell, Christian L / Allen, Todd M

2015 Volume 13, Page(s) 75–80

Abstract: Humanized mice are valuable models for the research and development of vaccine strategies and therapeutic interventions to control or eradicate HIV. The BLT humanized mouse model is particularly promising because the combination of transplantation of ... ...

Abstract	Humanized mice are valuable models for the research and development of vaccine strategies and therapeutic interventions to control or eradicate HIV. The BLT humanized mouse model is particularly promising because the combination of transplantation of human fetal pluripotent hematopoietic stem cells with surgical engraftment of human fetal thymic tissue results in improved T cell reconstitution, maturation, and selection. To date, the BLT humanized mouse model has been used to study many aspects of HIV infection including prevention, mucosal transmission, HIV-specific innate and adaptive immunity, viral latency, and novel antiretroviral and immune-based therapies for suppression and reservoir eradication. Here we describe recent advances and applications of the BLT humanized mouse model of HIV infection and discuss opportunities to further improve this valuable small animal model.
MeSH term(s)	Animals ; Disease Models, Animal ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/physiology ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/immunology ; Humans ; Mice ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation
Language	English
Publishing date	2015-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2015.05.002
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Article ; Online: Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection.

Garcia-Beltran, Wilfredo F / Claiborne, Daniel T / Maldini, Colby R / Phelps, Meredith / Vrbanac, Vladimir / Karpel, Marshall E / Krupp, Katharine L / Power, Karen A / Boutwell, Christian L / Balazs, Alejandro B / Tager, Andrew M / Altfeld, Marcus / Allen, Todd M

Frontiers in immunology

2021 Volume 12, Page(s) 667393

Abstract: Humanized bone marrow-liver-thymus (HuBLT) mice are a revolutionary small-animal model that has facilitated the study of human immune function and human-restricted pathogens, including human immunodeficiency virus type 1 (HIV-1). These mice recapitulate ... ...

Abstract	Humanized bone marrow-liver-thymus (HuBLT) mice are a revolutionary small-animal model that has facilitated the study of human immune function and human-restricted pathogens, including human immunodeficiency virus type 1 (HIV-1). These mice recapitulate many aspects of acute and chronic HIV-1 infection, but exhibit weak and variable T-cell responses when challenged with HIV-1, hindering our ability to confidently detect HIV-1-specific responses or vaccine effects. To identify the cause of this, we comprehensively analyzed T-cell development, diversity, and function in HuBLT mice. We found that virtually all HuBLT were well-reconstituted with T cells and had intact TCRβ sequence diversity, thymic development, and differentiation to memory and effector cells. However, there was poor CD4+ and CD8+ T-cell responsiveness to physiologic stimuli and decreased TH1 polarization that correlated with deficient reconstitution of innate immune cells, in particular monocytes. HIV-1 infection of HuBLT mice showed that mice with higher monocyte reconstitution exhibited greater CD8+ T cells responses and HIV-1 viral evolution within predicted HLA-restricted epitopes. Thus, T-cell responses to immune challenges are blunted in HuBLT mice due to a deficiency of innate immune cells, and future efforts to improve the model for HIV-1 immune response and vaccine studies need to be aimed at restoring innate immune reconstitution.
MeSH term(s)	Animals ; Biological Evolution ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Disease Models, Animal ; HIV Infections/immunology ; HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Immune Reconstitution ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Viremia
Language	English
Publishing date	2021-05-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.667393
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Article: Identification of HLA class I-associated amino acid polymorphisms in the HIV-1C proteome.

Boutwell, Christian L / Essex, M

AIDS research and human retroviruses

2007 Volume 23, Issue 1, Page(s) 165–174

Abstract: Human immunodeficiency virus type 1 (HIV-1) evasion of host cytotoxic T lymphocyte (CTL) targeting is linked to the expression of variant amino acid residues, or escape mutations, in positions that alter the normal processing, presentation, or ... ...

Abstract	Human immunodeficiency virus type 1 (HIV-1) evasion of host cytotoxic T lymphocyte (CTL) targeting is linked to the expression of variant amino acid residues, or escape mutations, in positions that alter the normal processing, presentation, or recognition of targeted epitopes. The combined genetic variability of HIV and the class I human leukocyte antigen (HLA) loci makes it difficult to characterize CTL escape mutations on a population level. However, a role in CTL escape may be inferred by identifying HIV amino acid polymorphisms that are specifically associated with particular HLA class I alleles. We describe here the results of a comprehensive analysis of HIV-1 subtype C (HIV-1C) to identify HLA class I-associated amino acid polymorphisms. We identified 94 HLA-associated amino acid polymorphisms distributed across the 15 major viral proteins analyzed. HLA-B alleles were involved in more associations (50%) than alleles from either the HLA-A (27%) or HLA-C (24%) loci. HLA-associated polymorphisms were identified in 18 of 26 previously described HIV-1C CTL immunoreactive regions including 7 of the 8 classified as immunodominant. Comparison to known HIV-1 CTL epitopes revealed that 19 of the HLA-associated polymorphisms were located in CTL epitopes restricted by the associated HLA allele. These results suggest that HIV-1C retains the potential for CTL escape across the entire proteome including regions that are broadly targeted on a population scale. The impact of CTL escape on natural and vaccine-induced CTL immunity warrants the continued characterization of the role of such HLA-associated polymorphisms in this process.
MeSH term(s)	Alleles ; Amino Acid Sequence ; HIV-1/classification ; HIV-1/genetics ; HIV-1/immunology ; HLA Antigens/classification ; HLA Antigens/genetics ; HLA Antigens/immunology ; Humans ; Linear Models ; Molecular Sequence Data ; Polymorphism, Genetic/genetics ; Polymorphism, Genetic/immunology ; Proteome ; Sequence Homology, Amino Acid
Chemical Substances	HLA Antigens ; Proteome
Language	English
Publishing date	2007-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/aid.2006.0131
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Article ; Online: Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo.

Maldini, Colby R / Claiborne, Daniel T / Okawa, Ken / Chen, Tao / Dopkin, Derrick L / Shan, Xiaochuan / Power, Karen A / Trifonova, Radiana T / Krupp, Katharine / Phelps, Meredith / Vrbanac, Vladimir D / Tanno, Serah / Bateson, Timothy / Leslie, George J / Hoxie, James A / Boutwell, Christian L / Riley, James L / Allen, Todd M

Nature medicine

2020 Volume 26, Issue 11, Page(s) 1776–1787

Abstract: An effective strategy to cure HIV will likely require a potent and sustained antiviral T cell response. Here we explored the utility of chimeric antigen receptor (CAR) T cells, expressing the CD4 ectodomain to confer specificity for the HIV envelope, to ... ...

Abstract	An effective strategy to cure HIV will likely require a potent and sustained antiviral T cell response. Here we explored the utility of chimeric antigen receptor (CAR) T cells, expressing the CD4 ectodomain to confer specificity for the HIV envelope, to mitigate HIV-induced pathogenesis in bone marrow, liver, thymus (BLT) humanized mice. CAR T cells expressing the 4-1BB/CD3-ζ endodomain were insufficient to prevent viral rebound and CD4
MeSH term(s)	Animals ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Monoclonal, Humanized/pharmacology ; Bone Marrow/immunology ; Bone Marrow/virology ; CD3 Complex/antagonists & inhibitors ; CD4 Antigens/administration & dosage ; CD4 Antigens/immunology ; Gene Expression Regulation/immunology ; HIV Envelope Protein gp41/antagonists & inhibitors ; HIV Envelope Protein gp41/immunology ; HIV Infections/immunology ; HIV Infections/pathology ; HIV Infections/therapy ; HIV Infections/virology ; HIV-1/immunology ; HIV-1/pathogenicity ; Humans ; Immunotherapy, Adoptive ; Liver/immunology ; Liver/virology ; Mice ; Peptide Fragments/antagonists & inhibitors ; Peptide Fragments/immunology ; Protein Domains/immunology ; Receptors, CXCR4/antagonists & inhibitors ; Receptors, CXCR4/immunology ; Receptors, Chimeric Antigen/administration & dosage ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Thymus Gland/immunology ; Thymus Gland/virology ; Tumor Necrosis Factor Receptor Superfamily, Member 9/antagonists & inhibitors
Chemical Substances	Antibodies, Monoclonal, Humanized ; CD3 Complex ; CD3 antigen, zeta chain ; CD4 Antigens ; CXCR4 protein, mouse ; HIV Envelope Protein gp41 ; Peptide Fragments ; Receptors, CXCR4 ; Receptors, Chimeric Antigen ; Tumor Necrosis Factor Receptor Superfamily, Member 9 ; peptide C34
Language	English
Publishing date	2020-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-020-1039-5
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Article ; Online: Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia.

Claiborne, Daniel T / Dudek, Timothy E / Maldini, Colby R / Power, Karen A / Ghebremichael, Musie / Seung, Edward / Mellors, Elizabeth F / Vrbanac, Vladimir D / Krupp, Katharine / Bisesi, Abigail / Tager, Andrew M / Knipe, David M / Boutwell, Christian L / Allen, Todd M

Journal of virology

2019 Volume 93, Issue 20

Abstract: BLT (bone marrow-liver-thymus) humanized mice, which reconstitute a functional human immune system, develop prototypic human virus-specific ... ...

Abstract	BLT (bone marrow-liver-thymus) humanized mice, which reconstitute a functional human immune system, develop prototypic human virus-specific CD8
MeSH term(s)	Acute Disease ; Animals ; Biological Evolution ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Disease Models, Animal ; HIV Infections/immunology ; HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/immunology ; Host-Pathogen Interactions ; Humans ; Immunization ; Mice ; Mice, Transgenic ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/virology ; Viral Load ; Viremia ; gag Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	gag Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2019-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00814-19
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Article ; Online: Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein.

Boutwell, Christian L / Rowley, Christopher F / Essex, M

Journal of virology

2008 Volume 83, Issue 6, Page(s) 2460–2468

Abstract: Cytotoxic-T-lymphocyte (CTL) escape mutations in human immunodeficiency viruses encode amino acid substitutions in positions that disrupt CTL targeting, thereby increasing virus survival and conferring a relative fitness benefit. However, it is now clear ...

Abstract	Cytotoxic-T-lymphocyte (CTL) escape mutations in human immunodeficiency viruses encode amino acid substitutions in positions that disrupt CTL targeting, thereby increasing virus survival and conferring a relative fitness benefit. However, it is now clear that CTL escape mutations can also confer a fitness cost, and there is increasing evidence to suggest that in some cases, e.g., escape from HLA-B57/B5801-restricted responses, the costs to the escape virus may affect the clinical course of infection. To quantify the magnitude of the costs of HLA-B57/B5801 escape, a highly sensitive dual-infection assay that uses synonymous nucleotide sequence tags to quantify viral relative replication capacity (RRC) was developed. We then asked whether such CTL escape mutations had an impact equivalent to that seen for a benchmark mutation, the M184V antiretroviral drug resistance mutation of reverse transcriptase (RRC(V184) = 0.86). To answer the question, the RRCs were quantified for escape mutations in three immunodominant HLA-B57/B5801 epitopes in capsid: A146P in IW9 (RRC(P146) = 0.91), A163G in KF11 (RRC(G163) = 0.89), and T242N in TW10 (RRC(N242) = 0.86). Individually, the impact of the escape mutations on RRC was comparable to that of M184V, while coexpression of the mutations resulted in substantial further reductions, with the maximum impact observed for the triple mutant (RRC(P146-G163-N242) = 0.62). By comparison to M184V, the magnitude of the reductions in RRC caused by the escape mutations, particularly when coexpressed, suggests that the costs of escape are sufficient to affect in vivo viral dynamics and may thus play a role in the protective effect associated with HLA-B57/B5801.
MeSH term(s)	Amino Acid Substitution/immunology ; Capsid Proteins/genetics ; Capsid Proteins/immunology ; Cell Line ; Epitopes/genetics ; Epitopes/immunology ; HIV-1/genetics ; HIV-1/immunology ; HIV-1/physiology ; HLA-B Antigens/immunology ; Humans ; Mutation, Missense ; T-Lymphocytes, Cytotoxic/immunology ; Virus Replication
Chemical Substances	Capsid Proteins ; Epitopes ; HLA-B Antigens ; HLA-B57 antigen
Language	English
Publishing date	2008-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01970-08
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Article: Improvement in allele-specific PCR assay with the use of polymorphism-specific primers for the analysis of minor variant drug resistance in HIV-1 subtype C.

Rowley, Christopher F / Boutwell, Christian L / Lockman, Shahin / Essex, M

Journal of virological methods

2008 Volume 149, Issue 1, Page(s) 69–75

Abstract: In recent years, highly sensitive assays have been developed that detect HIV-1 drug resistance mutations when present at less than 1% of the viral population. These assays are powerful tools when attempting to determine the clinical implications of these ...

Abstract	In recent years, highly sensitive assays have been developed that detect HIV-1 drug resistance mutations when present at less than 1% of the viral population. These assays are powerful tools when attempting to determine the clinical implications of these low level resistant virions after the administration of single-dose nevirapine. This report demonstrates that non-drug resistant polymorphisms in the primer-binding site for the allele-specific PCR (ASPCR) assay impact primer binding resulting in significant discrepancies in the assay's performance. Specifically, the use of a "universal" set of ASPCR primers caused an overestimation of the K103N (ntAAC) mutation at position 103 of reverse transcriptase when primer binding site polymorphisms resided close to the 3' end of the allele-specific primer. Drug resistance was predicted at values ranging from 0.69% to 7.69% for a sample containing only 1% resistance mutations and 3.35-31.84% for a sample containing 5% mutations. Conversely, the use of polymorphism-specific primers detected 1.15-1.36% and 5.20-5.71% resistance for the same 1% and 5% samples. The results demonstrate the need to account for sequence polymorphisms when designing and implementing this highly specific assay.
MeSH term(s)	Alleles ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Binding Sites ; Botswana ; DNA Primers ; Drug Resistance, Viral/genetics ; Female ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV Reverse Transcriptase/genetics ; HIV-1/drug effects ; HIV-1/genetics ; Humans ; Nevirapine/pharmacology ; Nevirapine/therapeutic use ; Polymerase Chain Reaction/methods ; Polymorphism, Genetic ; Reverse Transcriptase Inhibitors/pharmacology ; Reverse Transcriptase Inhibitors/therapeutic use
Chemical Substances	Anti-HIV Agents ; DNA Primers ; Reverse Transcriptase Inhibitors ; Nevirapine (99DK7FVK1H) ; HIV Reverse Transcriptase (EC 2.7.7.49)
Language	English
Publishing date	2008-03-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2008.01.005
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Article ; Online: Viral evolution and escape during acute HIV-1 infection.

Boutwell, Christian L / Rolland, Morgane M / Herbeck, Joshua T / Mullins, James I / Allen, Todd M

The Journal of infectious diseases

2010 Volume 202 Suppl 2, Page(s) S309–14

Abstract: The extensive genetic diversity of human immunodeficiency virus type 1 (HIV-1) presents a significant barrier to the development of an effective and durable HIV vaccine. This variability not only makes it difficult to identify the targets against which ... ...

Abstract	The extensive genetic diversity of human immunodeficiency virus type 1 (HIV-1) presents a significant barrier to the development of an effective and durable HIV vaccine. This variability not only makes it difficult to identify the targets against which immune responses should be directed, but it also confers on the virus the capacity for rapid escape from effective immune responses. Here, we describe recent investigations of the genetic diversity of HIV-1 at transmission and of the evolution of the virus as it adapts to the host immune environment during the acute phase of HIV-1 infection. These studies increase our understanding of the virology of the earliest stages of HIV-1 infection and provide critical insights into the mechanisms underlying viral replication and immune control of diverse HIV-1 strains. Such knowledge will inform the design of smarter, more effective vaccines capable of inducing immune control of HIV-1.
MeSH term(s)	Evolution, Molecular ; Genetic Variation ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; Humans ; Immune Evasion
Language	English
Publishing date	2010-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1086/655653
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Article ; Online: Ultrasensitive detection of minor drug-resistant variants for HIV after nevirapine exposure using allele-specific PCR: clinical significance.

Rowley, Christopher F / Boutwell, Christian L / Lee, Esther J / MacLeod, Iain J / Ribaudo, Heather J / Essex, M / Lockman, Shahin

AIDS research and human retroviruses

2010 Volume 26, Issue 3, Page(s) 293–300

Abstract: HIV-1 drug resistance mutations have been detected at low frequencies after single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT). We investigated the relationship between these "minor variant" NVP-resistant viruses and ... ...

Abstract	HIV-1 drug resistance mutations have been detected at low frequencies after single-dose nevirapine (sdNVP) for prevention of mother-to-child transmission (PMTCT). We investigated the relationship between these "minor variant" NVP-resistant viruses and clinical outcome with NVP-containing antiretroviral therapy (ART). An allele-specific quantitative PCR (ASPCR) assay was used to quantify the pre-ART frequency of K103N and Y181C in 26 women who had received sdNVP. The cohort was composed of 7 patients who experienced virologic failure and 19 control patients who maintained virologic suppression on NVP-containing ART; all were negative for resistance by standard genotyping. NVP resistance mutations were found in 17 of 26 (65%) patients using ASPCR. The frequency of NVP-resistant viruses ranged from 0.1% to 4.11%. Receiver operating characteristics (ROC) analysis identified a clinical threshold frequency of 0.19% for the ASPCR assay. Application of this threshold demonstrated minor variant resistance in 6 of 7 patients (86%) who failed treatment compared to 6 of 19 patients (32%) who were successful (OR = 13; 95% CI 1.27-133). ASPCR provides a means of detecting minor variant drug-resistant viruses that may impact subsequent treatment response. These data suggest a clinical role for highly sensitive assays to detect and quantify resistant viruses at low frequencies.
MeSH term(s)	Botswana ; Drug Resistance, Viral/drug effects ; Drug Resistance, Viral/genetics ; Female ; Gene Frequency ; Genetic Variation ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/genetics ; Humans ; Nevirapine/therapeutic use ; Polymerase Chain Reaction/methods ; Predictive Value of Tests ; Pregnancy ; Pregnancy Complications, Infectious/drug therapy ; Pregnancy Complications, Infectious/virology ; RNA, Viral/analysis ; RNA, Viral/genetics ; Retrospective Studies ; Reverse Transcriptase Inhibitors/therapeutic use ; Sensitivity and Specificity ; Time Factors ; Treatment Outcome
Chemical Substances	RNA, Viral ; Reverse Transcriptase Inhibitors ; Nevirapine (99DK7FVK1H)
Language	English
Publishing date	2010-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639130-8
ISSN	1931-8405 ; 0889-2229
ISSN (online)	1931-8405
ISSN	0889-2229
DOI	10.1089/aid.2009.0082
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Article ; Online: Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins.

Boutwell, Christian L / Carlson, Jonathan M / Lin, Tien-Ho / Seese, Aaron / Power, Karen A / Peng, Jian / Tang, Yanhua / Brumme, Zabrina L / Heckerman, David / Schneidewind, Arne / Allen, Todd M

Journal of virology

2013 Volume 87, Issue 7, Page(s) 3952–3965

Abstract: Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape- ... ...

Abstract	Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape-associated viral fitness costs and benefits. The observation that CTL escape mutations can carry an associated fitness cost in terms of reduced virus replication capacity (RC) suggests a fitness cost-benefit trade-off that could delay CTL escape and thereby prolong CD8 response effectiveness. However, our understanding of this potential fitness trade-off is limited by the small number of CTL escape mutations for which a fitness cost has been quantified. Here, we quantified the fitness cost of the 29 most common HIV-1B Gag CTL escape mutations using an in vitro RC assay. The majority (20/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. Notably, the reduction in RC was significantly greater for CTL escape mutations associated with protective HLA class I alleles than for those associated with nonprotective alleles. To speed the future evaluation of CTL escape costs, we also developed an in silico approach for inferring the relative impact of a mutation on RC based on its computed impact on protein thermodynamic stability. These data illustrate that the magnitude of CTL escape-associated fitness costs, and thus the barrier to CTL escape, varies widely even in the conserved Gag proteins and suggest that differential escape costs may contribute to the relative efficacy of CD8 responses.
MeSH term(s)	Cloning, Molecular ; DNA Primers/genetics ; Genetic Fitness/genetics ; Genetic Fitness/immunology ; HIV-1/immunology ; Humans ; Mutagenesis, Site-Directed ; Mutation/genetics ; Plasmids/genetics ; Real-Time Polymerase Chain Reaction ; T-Lymphocytes, Cytotoxic/immunology ; Thermodynamics ; Virus Replication/genetics ; gag Gene Products, Human Immunodeficiency Virus/genetics
Chemical Substances	DNA Primers ; gag Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2013-01-30
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.03233-12
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Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito