HIV-1 Vpu Interference with Innate Cell-mediated Immune Mechanisms

ABSTRACTVaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments.IMPORTANCEHost-pathogen interactionsin vivoinvolve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the functional properties of HIV-1-specific IgG, more studies are needed on the functional attributes of HIV-1-specific IgA, specifically for vaccine-elicited IgA. Characterization of the functional properties of HIV-1 Env-specific IgA monoclonal antibodies from human vaccine clinical trials are critical toward understanding the capacity of the host immune response to block HIV-1 acquisition.

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7. Persistent viruses

Viruses: A Very Short Introduction ◽

10.1093/actrade/9780198811718.003.0008 ◽

2018 ◽

pp. 75-91

Author(s):

Dorothy H. Crawford

Keyword(s):

Hepatitis Viruses ◽

Immune Mechanisms ◽

Persistent Viruses ◽

Immune Attack ◽

Life Threatening ◽

Asymptomatic Infections ◽

Immune Defences ◽

Hiv 1

‘Persistent viruses’ explains how some viruses have evolved strategies for overcoming immune mechanisms and survive inside their host for prolonged periods, even for a lifetime. Evasion strategies encompass three basic manoeuvres: finding a niche in which to hide from immune attack, manipulating immune processes to benefit the virus, and outwitting immune defences by mutating rapidly. Most persistent viruses have evolved to cause mild or even asymptomatic infections, since a life-threatening disease would not only be detrimental to the host, but would also deprive the virus of its home. The herpesvirus family, retrovirus family, HIV-1, and hepatitis viruses are described in detail.

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No Evidence for Consistent Virus-Specific Immunity in Simian Immunodeficiency Virus-Exposed, Uninfected Rhesus Monkeys

Journal of Virology ◽

10.1128/jvi.00822-07 ◽

2007 ◽

Vol 81 (22) ◽

pp. 12368-12374 ◽

Cited By ~ 50

Author(s):

Norman L. Letvin ◽

Srini S. Rao ◽

Vi Dang ◽

Adam P. Buzby ◽

Birgit Korioth-Schmitz ◽

...

Keyword(s):

Simian Immunodeficiency Virus ◽

Rhesus Monkeys ◽

Intracellular Cytokine Staining ◽

Cell Mediated Immunity ◽

Immune Mechanisms ◽

Immune Correlates ◽

Immunodeficiency Virus ◽

Mucosal Infection ◽

Exposed Uninfected ◽

Hiv 1

ABSTRACT Defining the immune correlates of the protection against human immunodeficiency virus type 1 (HIV-1) acquisition in individuals who are exposed to HIV-1 but do not become infected may provide important direction for the creation of an HIV-1 vaccine. We have employed the simian immunodeficiency virus (SIV)/rhesus monkey model to determine whether monkeys can be repeatedly exposed to a primate lentivirus by a mucosal route and escape infection and whether virus-specific immune correlates of protection from infection can be identified in uninfected monkeys. Five of 18 rhesus monkeys exposed 18 times by intrarectal inoculation to SIVmac251 or SIVsmE660 were resistant to infection, indicating that the exposed/uninfected phenotype can be reproduced in a nonhuman primate AIDS model. However, routine peripheral blood lymphocyte gamma interferon enzyme-linked immunospot (ELISPOT), tetramer, and intracellular cytokine staining assays, as well as cytokine-augmented ELISPOT and peptide-stimulated tetramer assays, failed to define a systemic antigen-specific cellular immune correlate to this protection. Further, local cell-mediated immunity could not be demonstrated by tetramer assays of these protected monkeys, and local humoral immunity was not associated with protection against acquisition of virus in another cohort of mucosally exposed monkeys. Therefore, resistance to mucosal infection in these monkeys may not be mediated by adaptive virus-specific immune mechanisms. Rather, innate immune mechanisms or an intact epithelial barrier may be responsible for protection against mucosal infection in this population of monkeys.

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Mother-to-Child Transmission of HIV-1: Strong Association With Certain Maternal HLA-B Alleles Independent of Viral Load Implicates Innate Immune Mechanisms

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/00126334-200406010-00002 ◽

2004 ◽

Vol 36 (2) ◽

pp. 659-670 ◽

Cited By ~ 40

Author(s):

Robert Winchester ◽

Jane Pitt ◽

Manhattan Charurat ◽

Laurence S. Magder ◽

Harald H. H. G??ring ◽

...

Keyword(s):

Viral Load ◽

Strong Association ◽

Innate Immune ◽

Mother To Child Transmission ◽

Child Transmission ◽

Immune Mechanisms ◽

Mother To Child ◽

Hiv 1

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Role of immune mechanisms in induction of HIV-1 broadly neutralizing antibodies

Current Opinion in Immunology ◽

10.1016/j.coi.2011.04.003 ◽

2011 ◽

Vol 23 (3) ◽

pp. 383-390 ◽

Cited By ~ 72

Author(s):

Laurent Verkoczy ◽

Garnett Kelsoe ◽

M Anthony Moody ◽

Barton F Haynes

Keyword(s):

Neutralizing Antibodies ◽

Broadly Neutralizing Antibodies ◽

Immune Mechanisms ◽

Hiv 1

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Ultrastructural observations of human monocytes infected with HIV-1

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084843 ◽

1991 ◽

Vol 49 ◽

pp. 108-109

Author(s):

James K. Koehler ◽

Steven G. Reed ◽

Joao S. Silva

Keyword(s):

Gradient Centrifugation ◽

Virus Production ◽

Human Monocyte ◽

Red Cross ◽

Human Monocytes ◽

Blood Monocytes ◽

Hiv Replication ◽

Electron Microscopic ◽

Ultrastructural Studies ◽

Hiv 1

As part of a larger study involving the co-infection of human monocyte cultures with HIV and protozoan parasites, electron microscopic observations were made on the course of HIV replication and infection in these cells. Although several ultrastructural studies of the cytopathology associated with HIV infection have appeared, few studies have shown the details of virus production in “normal,” human monocytes/macrophages, one of the natural targets of the virus, and suspected of being a locus of quiescent virus during its long latent period. In this report, we detail some of the interactions of developing virons with the membranes and organelles of the monocyte host.Peripheral blood monocytes were prepared from buffy coats (Portland Red Cross) by Percoll gradient centrifugation, followed by adherence to cover slips. 90-95% pure monocytes were cultured in RPMI with 5% non-activated human AB serum for four days and infected with 100 TCID50/ml of HIV-1 for four hours, washed and incubated in fresh medium for 14 days.

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