Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

AbstractDendritic cells (DCs) play an important role in viral infections both as initiators of immunity and as viral targets. Interaction between DCs and the innate-like CD1d-restricted natural killer T (NKT) cells results in the mutual activation of both cells and the subsequent initiation of cellular immune responses. Here, we show that HIV-1 inhibits the surface expression of CD1d in productively infected DCs and identify this as a novel activity of the HIV-1 vpu gene product. Interestingly, the viral protein U (Vpu) does not enhance constitutive CD1d endocytosis or induce rapid CD1d degradation. Instead, the Vpu protein interacts with CD1d and suppresses its recycling from endosomal compartments to the cell surface by retaining CD1d in early endosomes. This interference with the CD1d antigen presentation pathway strongly inhibits the ability of infected DCs to activate CD1d-restricted NKT cells. Given that the interaction with CD1d-expressing DCs is central to the ability of NKT cells to regulate immunity, these data suggest that interference with the CD1d antigen presentation pathway represents an HIV-1 strategy to evade innate cellular immune responses and imply a role for the innate-like CD1d-restricted NKT cells in the host defense against HIV-1.

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Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses

Journal of Virology ◽

10.1128/jvi.76.6.2817-2826.2002 ◽

2002 ◽

Vol 76 (6) ◽

pp. 2817-2826 ◽

Cited By ~ 69

Author(s):

Georg M. Lauer ◽

Tam N. Nguyen ◽

Cheryl L. Day ◽

Gregory K. Robbins ◽

Theresa Flynn ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

T Lymphocyte ◽

Viral Loads ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Cellular Immune ◽

Lymphocyte Responses ◽

Hiv 1

ABSTRACT Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8+- and CD4+-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8+-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8+-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative response against any HCV protein was found in these coinfected persons. These data demonstrate a major discordance in immune responses to two persistent RNA viruses. In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons.

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