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Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN- α Production

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ABSTRACT

A majority of adults without HIV infection and with a low risk of HIV-exposure have plasma IgG antibodies that enhance the rate and magnitude of HIV-induced interferon alpha (IFN-α) production. Fc-dependent IgG-HIV complexes induce IFN-α rapidly and in high titers in response to HIV concentrations that are too low to otherwise stimulate an effective IFN-α response. IFN-α promoting antibody (IPA) counters HIV-specific inhibition of IFN-α production, and compensates for the inherent delay in IFN-α production common to HIV infection and other viruses. Naturally occurring IPA has the potential to initiate a potent IFN-α response early in the course of HIV mucosal invasion in time to terminate infection prior to the creation of a pool of persistently infected cells. The current study adds IPA as a mediator of an Fc-dependent antiviral state capable of preventing HIV infection.

No MeSH data available.


Comparison of IFN-α quantification by biological and immune (ELISA) assays.HIV-induced IFN-α produced in cultures were measure using a bioassay (red circles) and a human IFN-α multi-subtype immunoassay (black triangles). The red and black lines are a computer generated best fit curve. Samples contained: pDC (#1), a low HIV concentration (#2), and individual plasma (#3–13).
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f5: Comparison of IFN-α quantification by biological and immune (ELISA) assays.HIV-induced IFN-α produced in cultures were measure using a bioassay (red circles) and a human IFN-α multi-subtype immunoassay (black triangles). The red and black lines are a computer generated best fit curve. Samples contained: pDC (#1), a low HIV concentration (#2), and individual plasma (#3–13).

Mentions: Immune-specific reactivity of IFN-α produced in pDC and PBMC cultures was examined by bioassay in A549 cells and by an IFN-α multi-subtype immunoassay. Both methodologies produced concordant results, with the bioassay reporting approximately 10-fold higher IFN-α titers (Fig. 5). Antiviral activity from pDCs and PBMCs induced by HIV in the presence of IPA from persons residing in the USA or Thailand were neutralized by >99% with sheep polyclonal antibody (Ab) to human IFN-α. No loss of antiviral activity occurred when IFN-α preparations were incubated with anti-IFNγ antibody (data not shown).


Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN- α Production
Comparison of IFN-α quantification by biological and immune (ELISA) assays.HIV-induced IFN-α produced in cultures were measure using a bioassay (red circles) and a human IFN-α multi-subtype immunoassay (black triangles). The red and black lines are a computer generated best fit curve. Samples contained: pDC (#1), a low HIV concentration (#2), and individual plasma (#3–13).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121582&req=5

f5: Comparison of IFN-α quantification by biological and immune (ELISA) assays.HIV-induced IFN-α produced in cultures were measure using a bioassay (red circles) and a human IFN-α multi-subtype immunoassay (black triangles). The red and black lines are a computer generated best fit curve. Samples contained: pDC (#1), a low HIV concentration (#2), and individual plasma (#3–13).
Mentions: Immune-specific reactivity of IFN-α produced in pDC and PBMC cultures was examined by bioassay in A549 cells and by an IFN-α multi-subtype immunoassay. Both methodologies produced concordant results, with the bioassay reporting approximately 10-fold higher IFN-α titers (Fig. 5). Antiviral activity from pDCs and PBMCs induced by HIV in the presence of IPA from persons residing in the USA or Thailand were neutralized by >99% with sheep polyclonal antibody (Ab) to human IFN-α. No loss of antiviral activity occurred when IFN-α preparations were incubated with anti-IFNγ antibody (data not shown).

View Article: PubMed Central - PubMed

ABSTRACT

A majority of adults without HIV infection and with a low risk of HIV-exposure have plasma IgG antibodies that enhance the rate and magnitude of HIV-induced interferon alpha (IFN-α) production. Fc-dependent IgG-HIV complexes induce IFN-α rapidly and in high titers in response to HIV concentrations that are too low to otherwise stimulate an effective IFN-α response. IFN-α promoting antibody (IPA) counters HIV-specific inhibition of IFN-α production, and compensates for the inherent delay in IFN-α production common to HIV infection and other viruses. Naturally occurring IPA has the potential to initiate a potent IFN-α response early in the course of HIV mucosal invasion in time to terminate infection prior to the creation of a pool of persistently infected cells. The current study adds IPA as a mediator of an Fc-dependent antiviral state capable of preventing HIV infection.

No MeSH data available.