Vpr is preferentially targeted by CTL during HIV-1 infection
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Vpr is preferentially targeted by CTL during HIV-1 infection. / HIV Study Collaboration.
In: J IMMUNOL, Vol. 167, No. 5, 01.09.2001, p. 2743-52.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Vpr is preferentially targeted by CTL during HIV-1 infection
AU - Altfeld, Marcus
AU - Addo, M M
AU - Eldridge, R L
AU - Yu, X G
AU - Thomas, S
AU - Khatri, A
AU - Strick, D
AU - Phillips, M N
AU - Cohen, G B
AU - Islam, S A
AU - Kalams, S A
AU - Brander, C
AU - Goulder, P J
AU - Rosenberg, E S
AU - Walker, B D
AU - HIV Study Collaboration
PY - 2001/9/1
Y1 - 2001/9/1
N2 - The HIV-1 accessory proteins Vpr, Vpu, and Vif are essential for viral replication, and their cytoplasmic production suggests that they should be processed for recognition by CTLs. However, the extent to which these proteins are targeted in natural infection, as well as precise CTL epitopes within them, remains to be defined. In this study, CTL responses against HIV-1 Vpr, Vpu, and Vif were analyzed in 60 HIV-1-infected individuals and 10 HIV-1-negative controls using overlapping peptides spanning the entire proteins. Peptide-specific IFN-gamma production was measured by ELISPOT assay and flow-based intracellular cytokine quantification. HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8(+) T cell lines. CD8(+) T cell responses against Vpr, Vpu, and Vif were found in 45%, 2%, and 33% of HIV-1-infected individuals, respectively. Multiple CTL epitopes were identified in functionally important regions of HIV-1 Vpr and Vif. Moreover, in infected individuals in whom the breadth of HIV-1-specific responses was assessed comprehensively, Vpr and p17 were the most preferentially targeted proteins per unit length by CD8(+) T cells. These data indicate that despite the small size of these proteins Vif and Vpr are frequently targeted by CTL in natural HIV-1 infection and contribute importantly to the total HIV-1-specific CD8(+) T cell responses. These findings will be important in evaluating the specificity and breadth of immune responses during acute and chronic infection, and in the design and testing of candidate HIV vaccines.
AB - The HIV-1 accessory proteins Vpr, Vpu, and Vif are essential for viral replication, and their cytoplasmic production suggests that they should be processed for recognition by CTLs. However, the extent to which these proteins are targeted in natural infection, as well as precise CTL epitopes within them, remains to be defined. In this study, CTL responses against HIV-1 Vpr, Vpu, and Vif were analyzed in 60 HIV-1-infected individuals and 10 HIV-1-negative controls using overlapping peptides spanning the entire proteins. Peptide-specific IFN-gamma production was measured by ELISPOT assay and flow-based intracellular cytokine quantification. HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8(+) T cell lines. CD8(+) T cell responses against Vpr, Vpu, and Vif were found in 45%, 2%, and 33% of HIV-1-infected individuals, respectively. Multiple CTL epitopes were identified in functionally important regions of HIV-1 Vpr and Vif. Moreover, in infected individuals in whom the breadth of HIV-1-specific responses was assessed comprehensively, Vpr and p17 were the most preferentially targeted proteins per unit length by CD8(+) T cells. These data indicate that despite the small size of these proteins Vif and Vpr are frequently targeted by CTL in natural HIV-1 infection and contribute importantly to the total HIV-1-specific CD8(+) T cell responses. These findings will be important in evaluating the specificity and breadth of immune responses during acute and chronic infection, and in the design and testing of candidate HIV vaccines.
KW - Amino Acid Sequence
KW - Case-Control Studies
KW - Epitopes/genetics
KW - Gene Products, vif/genetics
KW - Gene Products, vpr/genetics
KW - HIV Infections/immunology
KW - HIV-1/genetics
KW - Human Immunodeficiency Virus Proteins
KW - Humans
KW - In Vitro Techniques
KW - Molecular Sequence Data
KW - Peptide Fragments/genetics
KW - T-Lymphocytes, Cytotoxic/immunology
KW - Viral Regulatory and Accessory Proteins/genetics
KW - vif Gene Products, Human Immunodeficiency Virus
KW - vpr Gene Products, Human Immunodeficiency Virus
U2 - 10.4049/jimmunol.167.5.2743
DO - 10.4049/jimmunol.167.5.2743
M3 - SCORING: Journal article
C2 - 11509618
VL - 167
SP - 2743
EP - 2752
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 5
ER -