Role of human immunodeficiency virus (HIV)-specific T-cell immunity in control of dual HIV-1 and HIV-2 infection.
Progressive immune dysfunction and AIDS develop in most cases of human immunodeficiency virus type 1 (HIV-1) infection but in only 25 to 30% of persons with HIV-2 infection. However, the natural history and immunologic responses of individuals with dual HIV-1 and HIV-2 infection are largely undefined. Based on our previous findings, we hypothesized that among patients with dual infection the control of HIV-1 is associated with the ability to respond to HIV-2 Gag epitopes and to maintain HIV-specific CD4(+) T-cell responses. To test this, we compared the HIV-specific ex vivo IFN-gamma enzyme-linked immunospot (ELISPOT) assay responses of 19 dually infected individuals to those of persons infected with HIV-1 or HIV-2 only. Further, we assessed the functional profile of HIV Gag-specific CD4(+) and CD8(+) T cells from nine HIV dually infected patients by using a multicolor intracellular cytokine staining assay. As determined by ELISPOT assay, the magnitude and frequency of IFN-gamma-secreting T-cell responses to gene products of HIV-1 were higher than those to gene products of HIV-2 (2.64 versus 1.53 log(10) IFN-gamma spot-forming cells/10(6) cells [90% versus 63%, respectively].) Further, HIV-1 Env-, Gag-, and Nef- and HIV-2 Gag-specific responses were common; HIV-2 Nef-specific responses were rare. HIV-specific CD4(+) T helper responses were detected in nine of nine dually infected subjects, with the majority of these T cells producing gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and, to a lesser extent, interleukin-2. The HIV-1 plasma viral load was inversely correlated with HIV-2 Gag-specific IFN-gamma-/TNF-alpha-secreting CD4(+) and HIV-2 Gag-specific IFN-gamma-secreting CD8(+) T cells. In conclusion, the T-cell memory responses associated with containment of single HIV-1 and HIV-2 infection play a similar significant role in the immune control of dual HIV-1 and HIV-2 infection.
Zheng
Natalie N
NN
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
McElrath
M Juliana
MJ
Sow
Papa-Salif
PS
Hawes
Stephen E
SE
Diallo-Agne
Habibatou
H
Stern
Joshua E
JE
Li
Fusheng
F
Mesher
Andrew L
AL
Robinson
Akeliah D
AD
Gottlieb
Geoffrey S
GS
Huang
Yunda
Y
Kiviat
Nancy B
NB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017124:Conserved Sequence; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes; D005260:Female; D015693:Gene Products, nef / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load; D054311:nef Gene Products, Human Immunodeficiency Virus
D016207:Cytokines; D000939:Epitopes; D015693:Gene Products, nef; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; C514838:nef protein, Human immunodeficiency virus 2