AIDS Research Today is a free monthly online journal that collates and summarizes the latest research about AIDS, including details on testing, treatment, prevention, hiv, life expectancy.

A high-affinity inhibitor of human CD59 enhances complement-mediated virolysis of HIV-1: implications for treatment of HIV-1/AIDS.

Hu W, Yu Q, Hu N, Byrd D, Amet T, Shikuma C, Shiramizu B, Halperin JA, Qin X

Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.

Many pathogenic enveloped viruses, including HIV-1, escape complement-mediated virolysis by incorporating host cell regulators of complement activation into their own viral envelope. The presence of complement regulators including CD59 on the external surface of the viral envelope confers resistance to complement-mediated virolysis, which may explain why human pathogenic viruses such as HIV-1 are not neutralized by complement in human fluids, even in the presence of high Ab titers against the viral surface proteins. In this study, we report the development of a recombinant form of the fourth domain of the bacterial toxin intermedilysin (the recombinant domain 4 of intermedilysin [rILYd4]), a 114 aa protein that inhibits human CD59 function with high affinity and specificity. In the presence of rILYd4, HIV-1 virions derived from either cell lines or peripheral blood mononuclear cells of HIV-1-infected patients became highly sensitive to complement-mediated lysis activated by either anti-HIV-1 gp120 Abs or by viral infection-induced Abs present in the plasma of HIV-1-infected individuals. We also demonstrated that rILYd4 together with serum or plasma from HIV-1-infected patients as a source of anti-HIV-1 Abs and complement did not mediate complement-mediated lysis of either erythrocytes or peripheral blood mononuclear cells. These results indicate that rILYd4 may represent a novel therapeutic agent against HIV-1/AIDS.

Published 23 December 2009 in J Immunol, 184(1): 359-68.
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Articles on AIDS published 22 December 2009:

HLA-B*35-Px-mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses.   J Exp Med, 206(13): 2959-66.

A subset of HLA-B*35 alleles, B*35-Px, are strongly associated with accelerated HIV-1 disease progression for reasons that are not understood. Interestingly, the alternative set of B*35 subtypes, B*35-PY, have no detectable impact on HIV-1 disease outcomes, even though they can present identical HIV-1 epitopes as B*35-Px molecules. Thus, the differential impact of these alleles on HIV-1 disease progression may be unrelated to interactions with HIV-1-specific CD8(+) T cells. Here, we show that ... [Abstract] [Full-text]

Articles on AIDS published 18 December 2009:

Relevance of CD38 expression on CD8 T cells to evaluate antiretroviral therapy response in HIV-1-infected youths.   Scand J Immunol, 71(1): 45-51.

Surrogate markers for monitoring immuno-virological discordant responders, in addition to plasma viral load and CD4 cells, are still lacking. We assessed the diagnostic utility of CD38 expression on CD8 T cell assay, alone or in association with lymphocyte proliferation to mycotic antigens, in evaluating antiretroviral response. 28 vertically HIV-infected youths, 21 HAART- and seven 2 nucleotide reverse transcriptase inhibitors-treated, were enrolled in a retrospective study. Responders (57.1%) ... [Abstract] [Full-text]

Articles on AIDS published 2 December 2009:

HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.   Nat Genet, 41(12): 1290-4.

A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific ... [Abstract] [Full-text]

Articles on AIDS published 25 November 2009:

Differential survival benefit of universal HAART access in Brazil: a nation-wide comparison of injecting drug users versus men who have sex with men.   J Acquir Immune Defic Syndr, 52(5): 629-35.

OBJECTIVE: Brazil accounts for approximately 70% of injection drug users (IDUs) receiving highly active antiretroviral therapy (HAART) in low-income/middle-income countries. We evaluated the impact of HAART availability/access on AIDS-related mortality among IDUs versus men who have sex with men (MSM). DESIGN: Nation-wide analysis on Brazilian IDU and MSM diagnosed with AIDS in 2000-2006. METHODS: Four national information systems were linked, and Cox regression was used to assess impact of ... [Abstract] [Full-text]

Articles on AIDS published 12 November 2009:

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The enhanced-sensitivity Trofile assay (Monogram Biosciences) was used to retest coreceptor use at both study screening and study entry for 118 treatment-experienced subjects in AIDS Clinical Trials Group A5211 who had CCR5-tropic (R5) virus detected by the original Trofile assay at study screening. Among 90 recipients of vicriviroc, a significantly (P< .001) greater mean reduction in HIV-1 RNA was observed in 72 subjects with R5 virus versus 15 subjects reclassified as having ... [Abstract] [Full-text]

Articles on AIDS published 10 November 2009:

Clonal B-cell population in a reactive lymph node in acquired immunodeficiency syndrome.   Diagn Cytopathol, 37(12): 910-4.

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Articles on AIDS published 28 October 2009:

Myopericytoma in patients with AIDS: a new class of Epstein-Barr virus-associated tumor.   Am J Surg Pathol, 33(11): 1666-72.

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Articles on AIDS published 27 October 2009:

Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials.   Nat Rev Immunol, 9(10): 717-28.

Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficiency viruses. However, the lack of efficacy in a recent clinical trial calls for a re-evaluation of the scientific assumptions regarding the predictive value of using data generated from rhesus macaques as a ... [Abstract] [Full-text]

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