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Article ; Online: Vaccination reshapes the virus-specific T cell repertoire in unexposed adults.

Pan, Yi-Gen / Aiamkitsumrit, Benjamas / Bartolo, Laurent / Wang, Yifeng / Lavery, Criswell / Marc, Adam / Holec, Patrick V / Rappazzo, C Garrett / Eilola, Theresa / Gimotty, Phyllis A / Hensley, Scott E / Antia, Rustom / Zarnitsyna, Veronika I / Birnbaum, Michael E / Su, Laura F

Immunity

2021 Volume 54, Issue 6, Page(s) 1245–1256.e5

Abstract: We examined how baseline ... ...

Abstract	We examined how baseline CD4
MeSH term(s)	Adult ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Chlorocebus aethiops ; Humans ; Receptors, Antigen, T-Cell/immunology ; Vaccination/methods ; Vero Cells ; Yellow Fever/immunology ; Yellow Fever/virology ; Yellow Fever Vaccine/immunology ; Yellow fever virus/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Antigens, Viral ; Receptors, Antigen, T-Cell ; Yellow Fever Vaccine
Language	English
Publishing date	2021-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2021.04.023
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Article ; Online: Human Immunodeficiency Virus Type 1 Cellular Entry and Exit in the T Lymphocytic and Monocytic Compartments: Mechanisms and Target Opportunities During Viral Disease.

Aiamkitsumrit, Benjamas / Sullivan, Neil T / Nonnemacher, Michael R / Pirrone, Vanessa / Wigdahl, Brian

Advances in virus research

2015 Volume 93, Page(s) 257–311

Abstract: During the course of human immunodeficiency virus type 1 infection, a number of cell types throughout the body are infected, with the majority of cells representing CD4+ T cells and cells of the monocyte-macrophage lineage. Both types of cells express, ... ...

Abstract	During the course of human immunodeficiency virus type 1 infection, a number of cell types throughout the body are infected, with the majority of cells representing CD4+ T cells and cells of the monocyte-macrophage lineage. Both types of cells express, to varying levels, the primary receptor molecule, CD4, as well as one or both of the coreceptors, CXCR4 and CCR5. Viral tropism is determined by both the coreceptor utilized for entry and the cell type infected. Although a single virus may have the capacity to infect both a CD4+ T cell and a cell of the monocyte-macrophage lineage, the mechanisms involved in both the entry of the virus into the cell and the viral egress from the cell during budding and viral release differ depending on the cell type. These host-virus interactions and processes can result in the differential targeting of different cell types by selected viral quasispecies and the overall amount of infectious virus released into the extracellular environment or by direct cell-to-cell spread of viral infectivity. This review covers the major steps of virus entry and egress with emphasis on the parts of the replication process that lead to differences in how the virus enters, replicates, and buds from different cellular compartments, such as CD4+ T cells and cells of the monocyte-macrophage lineage.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/virology ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/physiology ; Humans ; Monocytes/virology ; Virus Internalization ; Virus Release
Language	English
Publishing date	2015
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	195-8
ISSN	1557-8399 ; 0065-3527
ISSN (online)	1557-8399
ISSN	0065-3527
DOI	10.1016/bs.aivir.2015.04.001
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Article ; Online: Bioinformatic analysis of HIV-1 entry and pathogenesis.

Aiamkitsumrit, Benjamas / Dampier, Will / Antell, Gregory / Rivera, Nina / Martin-Garcia, Julio / Pirrone, Vanessa / Nonnemacher, Michael R / Wigdahl, Brian

Current HIV research

2014 Volume 12, Issue 2, Page(s) 132–161

Abstract: The evolution of human immunodeficiency virus type 1 (HIV-1) with respect to co-receptor utilization has been shown to be relevant to HIV-1 pathogenesis and disease. The CCR5-utilizing (R5) virus has been shown to be important in the very early stages of ...

Abstract	The evolution of human immunodeficiency virus type 1 (HIV-1) with respect to co-receptor utilization has been shown to be relevant to HIV-1 pathogenesis and disease. The CCR5-utilizing (R5) virus has been shown to be important in the very early stages of transmission and highly prevalent during asymptomatic infection and chronic disease. In addition, the R5 virus has been proposed to be involved in neuroinvasion and central nervous system (CNS) disease. In contrast, the CXCR4-utilizing (X4) virus is more prevalent during the course of disease progression and concurrent with the loss of CD4(+) T cells. The dual-tropic virus is able to utilize both co-receptors (CXCR4 and CCR5) and has been thought to represent an intermediate transitional virus that possesses properties of both X4 and R5 viruses that can be encountered at many stages of disease. The use of computational tools and bioinformatic approaches in the prediction of HIV-1 co-receptor usage has been growing in importance with respect to understanding HIV-1 pathogenesis and disease, developing diagnostic tools, and improving the efficacy of therapeutic strategies focused on blocking viral entry. Current strategies have enhanced the sensitivity, specificity, and reproducibility relative to the prediction of co-receptor use; however, these technologies need to be improved with respect to their efficient and accurate use across the HIV-1 subtypes. The most effective approach may center on the combined use of different algorithms involving sequences within and outside of the env-V3 loop. This review focuses on the HIV-1 entry process and on co-receptor utilization, including bioinformatic tools utilized in the prediction of co-receptor usage. It also provides novel preliminary analyses for enabling identification of linkages between amino acids in V3 with other components of the HIV-1 genome and demonstrates that these linkages are different between X4 and R5 viruses.
MeSH term(s)	Computational Biology/methods ; HIV Infections/metabolism ; HIV Infections/pathology ; Humans ; Receptors, CCR5/metabolism ; Receptors, CXCR4/metabolism
Chemical Substances	Receptors, CCR5 ; Receptors, CXCR4
Language	English
Publishing date	2014-05-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2192348-6
ISSN	1873-4251 ; 1570-162X
ISSN (online)	1873-4251
ISSN	1570-162X
DOI	10.2174/1570162x12666140526121746
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Article: Evidence of Divergent Amino Acid Usage in Comparative Analyses of R5- and X4-Associated HIV-1 Vpr Sequences.

Antell, Gregory C / Dampier, Will / Aiamkitsumrit, Benjamas / Nonnemacher, Michael R / Pirrone, Vanessa / Zhong, Wen / Kercher, Katherine / Passic, Shendra / Williams, Jean / Liu, Yucheng / James, Tony / Jacobson, Jeffrey M / Szep, Zsofia / Wigdahl, Brian / Krebs, Fred C

International journal of genomics

2017 Volume 2017, Page(s) 4081585

Abstract: Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into ... ...

Abstract	Vpr is an HIV-1 accessory protein that plays numerous roles during viral replication, and some of which are cell type dependent. To test the hypothesis that HIV-1 tropism extends beyond the envelope into the
Language	English
Publishing date	2017-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2711883-6
ISSN	2314-4378 ; 2314-436X
ISSN (online)	2314-4378
ISSN	2314-436X
DOI	10.1155/2017/4081585
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Article ; Online: The receptor repertoire and functional profile of follicular T cells in HIV-infected lymph nodes.

Wendel, Ben S / Del Alcazar, Daniel / He, Chenfeng / Del Río-Estrada, Perla M / Aiamkitsumrit, Benjamas / Ablanedo-Terrazas, Yuria / Hernandez, Stefany M / Ma, Ke-Yue / Betts, Michael R / Pulido, Laura / Huang, Jun / Gimotty, Phyllis A / Reyes-Terán, Gustavo / Jiang, Ning / Su, Laura F

Science immunology

2018 Volume 3, Issue 22

Abstract: Follicular helper ... ...

Abstract	Follicular helper CD4
MeSH term(s)	Adolescent ; Adult ; Amino Acid Sequence ; Animals ; B-Lymphocytes/immunology ; Female ; HIV Infections/immunology ; Humans ; Interleukins/immunology ; Interleukins/metabolism ; Lymph Nodes/immunology ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; Young Adult
Chemical Substances	Interleukins ; Receptors, Antigen, T-Cell ; interleukin-21 (MKM3CA6LT1)
Language	English
Publishing date	2018-04-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.aan8884
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Article ; Online: Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures.

Antell, Gregory C / Dampier, Will / Aiamkitsumrit, Benjamas / Nonnemacher, Michael R / Jacobson, Jeffrey M / Pirrone, Vanessa / Zhong, Wen / Kercher, Katherine / Passic, Shendra / Williams, Jean W / Schwartz, Gregory / Hershberg, Uri / Krebs, Fred C / Wigdahl, Brian

Retrovirology

2016 Volume 13, Issue 1, Page(s) 32

Abstract: Background: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 ... ...

Abstract	Background: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures associated with co-receptor utilization. Results: The accessory protein Tat and the HlV-1 long terminal repeat (LTR) were analyzed with respect to genetic diversity and compared by Jensen-Shannon divergence which resulted in a correlation with both mean genetic diversity as well as the absolute difference in genetic diversity between R5- and X4-genome specific trends. As expected, the V3 domain of the gp120 protein was enriched with statistically divergent positions. Statistically divergent positions were also identified in Tat amino acid sequences within the transactivation and TAR-binding domains, and in nucleotide positions throughout the LTR. We further analyzed LTR sequences for putative transcription factor binding sites using the JASPAR transcription factor binding profile database and found several putative differences in transcription factor binding sites between R5 and X4 HIV-1 genomes, specifically identifying the C/EBP sites I and II, and Sp site III to differ with respect to sequence configuration for R5 and X4 LTRs. Conclusion: These observations support the hypothesis that co-receptor utilization coincides with specific genetic signatures in HIV-1 Tat and the LTR, likely due to differing transcriptional regulatory mechanisms and selective pressures applied within specific cellular targets during the course of productive HIV-1 infection.
MeSH term(s)	Binding Sites ; CD4 Antigens/metabolism ; Genetic Variation ; HIV Envelope Protein gp120/chemistry ; HIV Envelope Protein gp120/genetics ; HIV Long Terminal Repeat/genetics ; HIV-1/genetics ; HIV-1/physiology ; Humans ; Peptide Fragments/chemistry ; Peptide Fragments/genetics ; Receptors, CCR5/metabolism ; Receptors, CXCR4/metabolism ; Transcription Factors/metabolism ; Viral Tropism ; tat Gene Products, Human Immunodeficiency Virus/chemistry ; tat Gene Products, Human Immunodeficiency Virus/genetics
Chemical Substances	CD4 Antigens ; HIV Envelope Protein gp120 ; HIV envelope protein gp120 (305-321) ; Peptide Fragments ; Receptors, CCR5 ; Receptors, CXCR4 ; Transcription Factors ; tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2016-05-03
Publishing country	England
Document type	Journal Article
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/s12977-016-0266-9
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Article ; Online: HIV-1 Genetic Variation Resulting in the Development of New Quasispecies Continues to Be Encountered in the Peripheral Blood of Well-Suppressed Patients.

Dampier, Will / Nonnemacher, Michael R / Mell, Joshua / Earl, Joshua / Ehrlich, Garth D / Pirrone, Vanessa / Aiamkitsumrit, Benjamas / Zhong, Wen / Kercher, Katherine / Passic, Shendra / Williams, Jean W / Jacobson, Jeffrey M / Wigdahl, Brian

PloS one

2016 Volume 11, Issue 5, Page(s) e0155382

Abstract: As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, ...

Abstract	As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with respect to selection pressures such as therapeutic interventions, AIDS defining illnesses, and other factors. Phylogenetic methods based on the sequences of the LTR and tat exon 1 of the HIV-1 proviral DNA quasispecies were used to obtain an estimate of an average mutation rate of 5.3 nucleotides (nt)/kilobasepair (kb)/year (yr) prior to initiation of antiretroviral therapy (ART). Following ART the baseline mutation rate was reduced to an average of 1.02 nt/kb/yr. The post-ART baseline rate of genetic change, however, appears to be unique for each patient. These studies represent our initial steps in quantifying rates of genetic change among HIV-1 quasispecies using longitudinally sampled sequences from patients at different stages of disease both before and after initiation of combination ART. Notably, while long-term ART reduced the estimated mutation rates in the vast majority of patients studied, there was still measurable HIV-1 mutation even in patients with no detectable virus by standard quantitative assays. Determining the factors that affect HIV-1 mutation rates in the peripheral blood may lead to elucidation of the mechanisms associated with changes in HIV-1 disease severity.
MeSH term(s)	Adult ; Anti-HIV Agents/therapeutic use ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/cytology ; Cohort Studies ; DNA Mutational Analysis ; DNA, Viral/genetics ; Female ; Genetic Variation ; HIV Infections/blood ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/genetics ; Humans ; Male ; Middle Aged ; Mutation ; Phylogeny ; Polymerase Chain Reaction ; Viral Load
Chemical Substances	Anti-HIV Agents ; DNA, Viral
Language	English
Publishing date	2016-05-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0155382
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Article ; Online: Vaccination reshapes the virus-specific T cell repertoire in unexposed adults

Pan, Yi-Gen / Aiamkitsumrit, Benjamas / Bartolo, Laurent / Wang, Yifeng / Lavery, Criswell / Marc, Adam / Holec, Patrick V. / Rappazzo, C. Garrett / Eilola, Theresa / Gimotty, Phyllis A. / Hensley, Scott E. / Antia, Rustom / Zarnitsyna, Veronika I. / Birnbaum, Michael E. / Su, Laura F.

bioRxiv

Abstract: How baseline T cell characteristics impact human T cell responses to novel pathogens remains unknown. Here, we address this question by studying the CD4+ T cell response in unexposed individuals to live attenuated yellow fever virus (YFV) vaccine. We ... ...

Abstract	How baseline T cell characteristics impact human T cell responses to novel pathogens remains unknown. Here, we address this question by studying the CD4+ T cell response in unexposed individuals to live attenuated yellow fever virus (YFV) vaccine. We quantified virus-specific population dynamics over time using class II peptide-MHC tetramers. Our data revealed that, even in the absence of known viral exposure, memory phenotype T cells were found in the majority of virus-specific precursors in healthy adults. Pre-existing memory T cells can be divided into two groups; abundant pre-vaccine populations that underwent limited overall expansion and rare cells that generated naïve-like responses and preferentially contributed to the memory repertoire after vaccination. Single cell T cell receptor (TCR) sequencing was used to track the evolution of immune responses to different epitopes and showed an association between preservation of unexpanded TCRs before exposure and the robustness of post-vaccine responses. Instead of a further increase in pre-established TCR clones, vaccination boosted the representation of rare TCRs. Thus, vaccine restructures the abundance and clonal hierarchy of virus-specific T cells. Our results link T cell precursor states to post-exposure responses, identifying peripheral education of virus-specific repertoire as a key component of effective vaccination. ∘ YFV-specific precursors contain abundant memory phenotype cells in healthy adults. ∘ Precursor frequency and phenotype are linked to post-immune response. ∘ Vaccination recruits rare virus-specific populations. ∘ Vaccination overrides pre-established clonal hierarchy
Keywords	covid19
Publisher	BioRxiv
Document type	Article ; Online
DOI	10.1101/2020.10.01.322958
Database	COVID19

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Article ; Online: Impact of Tat Genetic Variation on HIV-1 Disease.

Li, Luna / Dahiya, Satinder / Kortagere, Sandhya / Aiamkitsumrit, Benjamas / Cunningham, David / Pirrone, Vanessa / Nonnemacher, Michael R / Wigdahl, Brian

Advances in virology

2012 Volume 2012, Page(s) 123605

Abstract: The human immunodeficiency virus type 1 (HIV-1) promoter or long-terminal repeat (LTR) regulates viral gene expression by interacting with multiple viral and host factors. The viral transactivator protein Tat plays an important role in transcriptional ... ...

Abstract	The human immunodeficiency virus type 1 (HIV-1) promoter or long-terminal repeat (LTR) regulates viral gene expression by interacting with multiple viral and host factors. The viral transactivator protein Tat plays an important role in transcriptional activation of HIV-1 gene expression. Functional domains of Tat and its interaction with transactivation response element RNA and cellular transcription factors have been examined. Genetic variation within tat of different HIV-1 subtypes has been shown to affect the interaction of the viral transactivator with cellular and/or viral proteins, influencing the overall level of transcriptional activation as well as its action as a neurotoxic protein. Consequently, the genetic variability within tat may impact the molecular architecture of functional domains of the Tat protein that may impact HIV pathogenesis and disease. Tat as a therapeutic target for anti-HIV drugs has also been discussed.
Language	English
Publishing date	2012-07-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625776-2
ISSN	1687-8647 ; 1687-8647
ISSN (online)	1687-8647
ISSN	1687-8647
DOI	10.1155/2012/123605
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Article ; Online: Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status.

Dampier, Will / Antell, Gregory C / Aiamkitsumrit, Benjamas / Nonnemacher, Michael R / Jacobson, Jeffrey M / Pirrone, Vanessa / Zhong, Wen / Kercher, Katherine / Passic, Shendra / Williams, Jean W / James, Tony / Devlin, Kathryn N / Giovannetti, Tania / Libon, David J / Szep, Zsofia / Ehrlich, Garth D / Wigdahl, Brian / Krebs, Fred C

Journal of neurovirology

2017 Volume 23, Issue 1, Page(s) 113–124

Abstract: Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV- ... ...

Abstract	Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS). Our studies revealed unique associations between GDS and the presence of specific amino acid changes in peripheral blood-derived Vpr sequences [neuropsychological impairment Vpr (niVpr) variants]. Amino acids N41 and A55 in the Vpr sequence were associated with more pronounced neurocognitive deficits (higher GDS). In contrast, amino acids I37 and S41 were connected to measurably lower GDS. All niVpr variants were also detected in DNA isolated from HIV-1-infected brain tissues. The implication of these results is that niVpr variants alter the genesis and/or progression of HAND through differences in Vpr-mediated effects in the peripheral blood and/or the brain.
Language	English
Publishing date	2017-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1007/s13365-016-0462-3
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