Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2007 Sep;81(17):9061-71.
doi: 10.1128/JVI.00117-07. Epub 2007 Jun 20.

Role of human immunodeficiency virus (HIV)-specific T-cell immunity in control of dual HIV-1 and HIV-2 infection

Natalie N Zheng  1 , M Juliana McElrath, Papa-Salif Sow, Stephen E Hawes, Habibatou Diallo-Agne, Joshua E Stern, Fusheng Li, Andrew L Mesher, Akeliah D Robinson, Geoffrey S Gottlieb, Yunda Huang, Nancy B Kiviat
Affiliations
Comparative Study

Role of human immunodeficiency virus (HIV)-specific T-cell immunity in control of dual HIV-1 and HIV-2 infection

Natalie N Zheng et al. J Virol. 2007 Sep.

Abstract

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.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Frequency, magnitude, and breadth of IFN-γ secreting T-cell recognizing HIV peptides within Gag, Env, Nef, and Tat among subjects with dual HIV-1 and HIV-2 infection (n = 19). (A) Frequency of IFN-γ T-cell responses recognizing Gag, Env, Nef, Tat, and any gene product of HIV-1 only, HIV-2 only, both HIV-1 and HIV-2, or neither. (B) Magnitude of IFN-γ T-cell responses to HIV-1 and HIV-2 peptides recognizing epitopes within Gag, Env, Nef, and Tat. The magnitude of total (any) HIV-1 responses was significantly greater than the median magnitude of total HIV-2 responses (2.64 log10 compared to 1.53 log10 SFC/106, respectively [*, P = 0.002]). This difference was mostly a result of significantly increased levels of Nef responses in HIV-1 compared to HIV-2 (1.88 log10 versus 0 log10 SFC/106, respectively [**, P < 0.0001]). —, Median of responses. (C) Breadth of responses to HIV-1 and HIV-2 gene products. *, Patient 19 had no detectable HIV-1- or HIV-2-specific responses.
FIG. 2.
FIG. 2.
Cytokine profile of CD4+ (A) and CD8+ (B) T-cell responses recognizing HIV Gag- and CMV pp56 in HIV-1/2 dually infected subjects (n = 9). Antigen-specific responses of >0.02% of the total CD4+ or CD8+ T cells producing each cytokine were considered positive. Each pie chart represents the mean responses of all subjects to the HIV-1, HIV-2 Gag, and CMV pp56 overlapping 15 mers. Responses are grouped by cytokines secreted and matched to the pattern in the legend. The arc outside the pie chart indicates the mean percentage of HIV-1-, HIV-2-, or CMV-specific IFN-γ (blue)-, IL-2 (red)-, or TNF-α (green)-producing cells. The dot plots represent the mean magnitude of response to CMV, HIV-1, and HIV-2 Gag with multiple functional cytokine profile indicated in the legend. Each “+” in the legend denotes IFN-γ, IL-2, and TNF-α positivity.
FIG. 3.
FIG. 3.
Negative correlation between the frequencies of HIV-2 Gag-specific IFN-γ+ or TNF-α+ CD4+ (A) and IFN-γ+ CD8+ (B) T cells with HIV-1 plasma viral load in dually infected subjects. A Spearman ranking test was used to analyze the correlation. Positive responses were designated when the percentage of bright cytokine+ CD4+ or CD8+ T cells was twice that of the negative control and >0.02% of the total CD4+ or CD8+ T cells. Antigen-specific responses of <0.01% are shown as 0.01% on the figures.
FIG. 4.
FIG. 4.
IFN-γ responses to epitopes at the conserved region between HIV-1 and HIV-2 Gag. (A) Amino acid conservation between HIV-1 and HIV-2 Gag. A schematic diagram shows the functional domains in the HIV-1 and HIV-2 Gag. The sequence conservation of every nine amino acid sequence in HIV-2 Gag (Rod) was compared to all of the HIV-1 subtype CRF-02 Gag sequences available in the HIV-1 database at the same position. Amino acid sequences at seven regions in HIV-1 and HIV-2 share 36 to 94% similarity. (B) Position and amino acid sequence at the conserved regions between HIV-1 and HIV-2. Amino acids that differ between HIV-1 and HIV-2 at the conserved region are highlighted in red). (C) Detection of cross-reactive responses to epitopes at the conserved regions between HIV-1 and HIV-2 Gag. The line shows the cutoff of positive responses (at 100 SFC/106 PBMC).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Alabi, A. S., S. Jaffar, K. Ariyoshi, T. Blanchard, M. Schim van der Loeff, A. A. Awasana, T. Corrah, S. Sabally, R. Sarge-Njie, F. Cham-Jallow, A. Jaye, N. Berry, and H. Whittle. 2003. Plasma viral load, CD4 cell percentage, HLA and survival of HIV-1, HIV-2, and dually infected Gambian patients. AIDS 17:1513-1520. - PubMed
    1. Andersson, S., H. Norrgren, Z. da Silva, A. Biague, S. Bamba, S. Kwok, C. Christopherson, G. Biberfeld, and J. Albert. 2000. Plasma viral load in HIV-1 and HIV-2 singly and dually infected individuals in Guinea-Bissau, West Africa: significantly lower plasma virus set point in HIV-2 infection than in HIV-1 infection. Arch. Intern. Med. 160:3286-3293. - PubMed
    1. Anonymous. 1993. Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morb. Mortal. Wkly. Rep. Recomm. Rep. 41:1-19. - PubMed
    1. Betts, M. R., M. C. Nason, S. M. West, S. C. De Rosa, S. A. Migueles, J. Abraham, M. M. Lederman, J. M. Benito, P. A. Goepfert, M. Connors, M. Roederer, and R. A. Koup. 2006. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107:4781-4789. - PMC - PubMed
    1. Bourgeois, C., B. Rocha, and C. Tanchot. 2002. A role for CD40 expression on CD8+ T cells in the generation of CD8+ T-cell memory. Science 297:2060-2063. - PubMed

Publication types

MeSH terms