scholarly journals Conservation of cytotoxic T lymphocyte (CTL) epitopes as a host strategy to constrain parasite adaptation: evidence from the nef gene of human immunodeficiency virus 1 (HIV-1)

1998 ◽  
Vol 15 (10) ◽  
pp. 1259-1268 ◽  
Author(s):  
J. da Silva ◽  
A. L. Hughes
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Ctl Epitopes ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

scholarly journals Clustering Patterns of Cytotoxic T-Lymphocyte Epitopes in Human Immunodeficiency Virus Type 1 (HIV-1) Proteins Reveal Imprints of Immune Evasion on HIV-1 Global Variation

2002 ◽  
Vol 76 (17) ◽  
pp. 8757-8768 ◽  
Author(s):  
Karina Yusim ◽  
Can Kesmir ◽  
Brian Gaschen ◽  
Marylyn M. Addo ◽  
Marcus Altfeld ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Amino Acid Sequences ◽  
Ctl Epitopes ◽  
Ctl Epitope ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human cytotoxic T-lymphocyte (CTL) response to human immunodeficiency virus type 1 (HIV-1) has been intensely studied, and hundreds of CTL epitopes have been experimentally defined, published, and compiled in the HIV Molecular Immunology Database. Maps of CTL epitopes on HIV-1 protein sequences reveal that defined epitopes tend to cluster. Here we integrate the global sequence and immunology databases to systematically explore the relationship between HIV-1 amino acid sequences and CTL epitope distributions. CTL responses to five HIV-1 proteins, Gag p17, Gag p24, reverse transcriptase (RT), Env, and Nef, have been particularly well characterized in the literature to date. Through comparing CTL epitope distributions in these five proteins to global protein sequence alignments, we identified distinct characteristics of HIV amino acid sequences that correlate with CTL epitope localization. First, experimentally defined HIV CTL epitopes are concentrated in relatively conserved regions. Second, the highly variable regions that lack epitopes bear cumulative evidence of past immune escape that may make them relatively refractive to CTLs: a paucity of predicted proteasome processing sites and an enrichment for amino acids that do not serve as C-terminal anchor residues. Finally, CTL epitopes are more highly concentrated in alpha-helical regions of proteins. Based on amino acid sequence characteristics, in a blinded fashion, we predicted regions in HIV regulatory and accessory proteins that would be likely to contain CTL epitopes; these predictions were then validated by comparison to new sets of experimentally defined epitopes in HIV-1 Rev, Tat, Vif, and Vpr.

scholarly journals Rabies Virus-Based Vectors Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Envelope Protein Induce a Strong, Cross-Reactive Cytotoxic T-Lymphocyte Response against Envelope Proteins from Different HIV-1 Isolates

2001 ◽  
Vol 75 (9) ◽  
pp. 4430-4434 ◽  
Author(s):  
James P. McGettigan ◽  
Heather D. Foley ◽  
Igor M. Belyakov ◽  
Jay A. Berzofsky ◽  
Roger J. Pomerantz ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Rabies Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Lymphocyte ◽  
Envelope Protein ◽  
Cytotoxic T Lymphocyte ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Novel viral vectors that are able to induce both strong and long-lasting immune responses may be required as effective vaccines for human immunodeficiency virus type 1 (HIV-1) infection. Our previous experiments with a replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from a laboratory-adapted HIV-1 strain (NL4–3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we report that cytotoxic T-lymphocyte (CTL) responses against HIV-1 gp160 are induced by recombinant RVs. Our results indicated that a single inoculation of mice with an RV expressing HIV-1 gp160 induced a solid and long-lasting memory CTL response specific for HIV-1 envelope protein. Moreover, CTLs from immunized mice were not restricted to the homologous HIV-1 envelope protein and were able to cross-kill target cells expressing HIV-1 gp160 from heterologous HIV-1 strains. These studies further suggest promise for RV-based vectors to elicit a persistent immune response against HIV-1 and their potential utility as efficacious anti-HIV-1 vaccines.

scholarly journals Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection

2005 ◽  
Vol 79 (18) ◽  
pp. 12100-12105 ◽  
Author(s):  
Thillagavathie Pillay ◽  
Hua-Tang Zhang ◽  
Jan W. Drijfhout ◽  
Nicola Robinson ◽  
Helen Brown ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Escape ◽  
Immunodeficiency Virus ◽  
Ctl Escape ◽  
Hiv 1

ABSTRACT The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.

scholarly journals Persistent Antibody Responses but Declining Cytotoxic T-Lymphocyte Responses to Multiple Human Immunodeficiency Virus Type 1 Antigens in a Long-Term Nonprogressing Individual with a Defective p17 Proviral Sequence and No Detectable Viral RNA Expression

1998 ◽  
Vol 72 (4) ◽  
pp. 3472-3474 ◽  
Author(s):  
James M. Binley ◽  
Xia Jin ◽  
Yaoxing Huang ◽  
Linqi Zhang ◽  
Yunzhen Cao ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antibody Responses ◽  
The Past ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Long-term nonprogressor AD-18 has been infected with human immunodeficiency virus type 1 (HIV-1) for at least 16 years. During the past 5 years, he has had undetectable levels of plasma viremia, and HIV-1 cannot be isolated from him. Sequencing of proviral DNA indicates that the only HIV-1 sequences that can be identified in AD-18 have gross defects in the p17-encoding regions of the gag gene (Y. Huang, L. Zhang, and D. D. Ho, Virology 240:36–49, 1998). However, AD-18 has strong, sustained antibody responses to several HIV-1 antigens, including p17. Cytotoxic T-lymphocyte responses to Env and Gag antigens have gradually diminished over the past 4 years, at a time when the titers of antibodies to the same proteins have remained stable. We discuss what these observations might mean for the generation and maintenance of immunological memory.

scholarly journals Cross-Reactions between the Cytotoxic T-Lymphocyte Responses of Human Immunodeficiency Virus-Infected African and European Patients

1998 ◽  
Vol 72 (5) ◽  
pp. 3547-3553 ◽  
Author(s):  
Deniz Durali ◽  
Jacques Morvan ◽  
Franck Letourneur ◽  
Doris Schmitt ◽  
Nelly Guegan ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Recombinant Virus ◽  
Cytotoxic T Lymphocyte ◽  
Target Cells ◽  
Cross Reactions ◽  
Immunodeficiency Virus ◽  
The Impact ◽  
Hiv 1

ABSTRACT The great variability of protein sequences from human immunodeficiency virus (HIV) type 1 (HIV-1) isolates represents a major obstacle to the development of an effective vaccine against this virus. The surface protein (Env), which is the predominant target of neutralizing antibodies, is particularly variable. Here we examine the impact of variability among different HIV-1 subtypes (clades) on cytotoxic T-lymphocyte (CTL) activities, the other major component of the antiviral immune response. CTLs are produced not only against Env but also against other structural proteins, as well as some regulatory proteins. The genetic subtypes of HIV-1 were determined for Env and Gag from several patients infected either in France or in Africa. The cross-reactivities of the CTLs were tested with target cells expressing selected proteins from HIV-1 isolates of clade A or B or from HIV type 2 isolates. All African patients were infected with viruses belonging to clade A for Env and for Gag, except for one patient who was infected with a clade A Env-clade G Gag recombinant virus. All patients infected in France were infected with clade B viruses. The CTL responses obtained from all the African and all the French individuals tested showed frequent cross-reactions with proteins of the heterologous clade. Epitopes conserved between the viruses of clades A and B appeared especially frequent in Gag p24, Gag p18, integrase, and the central region of Nef. Cross-reactivity also existed among Gag epitopes of clades A, B, and G, as shown by the results for the patient infected with the clade A Env-clade G Gag recombinant virus. These results show that CTLs raised against viral antigens from different clades are able to cross-react, emphasizing the possibility of obtaining cross-immunizations for this part of the immune response in vaccinated individuals.

scholarly journals Levels of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Effector and Memory Responses Decline after Suppression of Viremia with Highly Active Antiretroviral Therapy

1999 ◽  
Vol 73 (8) ◽  
pp. 6721-6728 ◽  
Author(s):  
Spyros A. Kalams ◽  
Philip J. Goulder ◽  
Amy K. Shea ◽  
Norman G. Jones ◽  
Alicja K. Trocha ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Highly Active Antiretroviral Therapy ◽  
Cytotoxic T Lymphocyte ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) replication may help elucidate interactions between the host cellular immune responses and HIV-1 infection. We performed a detailed longitudinal evaluation of two subjects before and after the start of highly active antiretroviral therapy (HAART). Both subjects had evidence of in vivo-activated and memory cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1 gene products. After the start of therapy, both subjects had declines in the levels of in vivo-activated HIV-1-specific CTLs and had immediate increases in circulating HIV-1-specific CTL memory cells. With continued therapy, and continued suppression of viral load, levels of memory CTLps declined. HLA A*0201 peptide tetramer staining demonstrated that declining levels of in vivo-activated CTL activity were associated with a decrease in the expression of the CD38+ activation marker. Transient increases in viral load during continued therapy were associated with increases in the levels of virus-specific CTLps in both individuals. The results were confirmed by measuring CTL responses to discrete optimal epitopes. These studies illustrate the dynamic equilibrium between the host immune response and levels of viral antigen burden and suggest that efforts to augment HIV-1-specific immune responses in subjects on HAART may decrease the incidence of virologic relapse.

scholarly journals Induction of a Mucosal Cytotoxic T-Lymphocyte Response by Intrarectal Immunization with a Replication-Deficient Recombinant Vaccinia Virus Expressing Human Immunodeficiency Virus 89.6 Envelope Protein

1998 ◽  
Vol 72 (10) ◽  
pp. 8264-8272 ◽  
Author(s):  
Igor M. Belyakov ◽  
Linda S. Wyatt ◽  
Jeffrey D. Ahlers ◽  
Patricia Earl ◽  
C. David Pendleton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Vaccinia Virus ◽  
T Lymphocyte ◽  
Envelope Protein ◽  
Cytotoxic T Lymphocyte ◽  
Recombinant Vaccinia Virus ◽  
Mucosal Immunization ◽  
Recombinant Vaccinia ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT To improve the safety of recombinant vaccinia virus vaccines, modified vaccinia virus Ankara (MVA) has been employed, because it has a replication defect in most mammalian cells. Here we apply MVA to human immunodeficiency virus type 1 (HIV-1) vaccine development by incorporating the envelope protein gp160 of HIV-1 primary isolate strain 89.6 (MVA 89.6) and use it to induce mucosal cytotoxic-T-lymphocyte (CTL) immunity. In initial studies to define a dominant CTL epitope for HIV-1 89.6 gp160, we mapped the epitope to a sequence, IGPGRAFYAR (from the V3 loop), homologous to that recognized by HIV MN loop-specific CTL and showed that HIV-1 MN-specific CTLs cross-reactively recognize the corresponding epitope from strain 89.6 presented by H-2Dd. Having defined the CTL specificity, we immunized BALB/c mice intrarectally with recombinant MVA 89.6. A single mucosal immunization with MVA 89.6 was able to elicit long-lasting antigen-specific mucosal (Peyer’s patch and lamina propria) and systemic (spleen) CTL responses as effective as or more effective than those of a replication-competent vaccinia virus expressing 89.6 gp160. Immunization with MVA 89.6 led to (i) the loading of antigen-presenting cells in vivo, as measured by the ex vivo active presentation of the P18-89.6 peptide to an antigen-specific CTL line, and (ii) the significant production of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) in the mucosal sites. These results indicate that nonreplicating recombinant MVA may be at least as effective for mucosal immunization as replicating recombinant vaccinia virus.

scholarly journals Association between Virus-Specific Cytotoxic T-Lymphocyte and Helper Responses in Human Immunodeficiency Virus Type 1 Infection

1999 ◽  
Vol 73 (8) ◽  
pp. 6715-6720 ◽  
Author(s):  
Spyros A. Kalams ◽  
S. P. Buchbinder ◽  
E. S. Rosenberg ◽  
J. M. Billingsley ◽  
D. S. Colbert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cell Counts ◽  
Wide Range ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development.

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