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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.

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Effects of FcR Blockade and Chloroquine on IFN-α induced by HIV in the Presence of IPA.(A) Individual plasma was added along with a minimally stimulatory HIV concentration to either PBMC alone or PBMC pretreated with FcR Blocking Reagent or with 10 μM Chloroquine. Individual Thai and USA plasma are indicated by numbers 1, 2, 3 and 4, 5, 6 respectively. (*) denotes an IFN-α stimulatory concentration. (B) IFN-γ induced by PHA in either PBMC alone or pretreated with FcR Blocking Reagent or Chloroquine (10 μM). Samples with no IFN-α titer are represented by a single line.
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f6: Effects of FcR Blockade and Chloroquine on IFN-α induced by HIV in the Presence of IPA.(A) Individual plasma was added along with a minimally stimulatory HIV concentration to either PBMC alone or PBMC pretreated with FcR Blocking Reagent or with 10 μM Chloroquine. Individual Thai and USA plasma are indicated by numbers 1, 2, 3 and 4, 5, 6 respectively. (*) denotes an IFN-α stimulatory concentration. (B) IFN-γ induced by PHA in either PBMC alone or pretreated with FcR Blocking Reagent or Chloroquine (10 μM). Samples with no IFN-α titer are represented by a single line.

Mentions: IFN-α production promoted by Thai plasma (samples 1–3) and USA (samples 4–6) individuals were inhibited to undetectable levels in the presence of the endosomal alkalinizing agent chloroquine (Fig. 6). Additionally, IPA mediated HIV induced IFN-α production was reduced to undetectable levels when PBMCs were pre-incubated with an FcR blockade reagent containing a mixture of antibodies that block surface Fcγ receptors (Fig. 6). The combination of blocking antibodies had no effect on PBMC to produce the FcγR-independent induction of IFN-γ by phytohaemagglutinin (PHA), while chloroquine inhibited interferon induction consistent with the known dependency of interferon production on endosomal processing2526. Figure 6 is representative of three separate experiments.


Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals Promotes HIV-Induced IFN- α Production
Effects of FcR Blockade and Chloroquine on IFN-α induced by HIV in the Presence of IPA.(A) Individual plasma was added along with a minimally stimulatory HIV concentration to either PBMC alone or PBMC pretreated with FcR Blocking Reagent or with 10 μM Chloroquine. Individual Thai and USA plasma are indicated by numbers 1, 2, 3 and 4, 5, 6 respectively. (*) denotes an IFN-α stimulatory concentration. (B) IFN-γ induced by PHA in either PBMC alone or pretreated with FcR Blocking Reagent or Chloroquine (10 μM). Samples with no IFN-α titer are represented by a single line.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Effects of FcR Blockade and Chloroquine on IFN-α induced by HIV in the Presence of IPA.(A) Individual plasma was added along with a minimally stimulatory HIV concentration to either PBMC alone or PBMC pretreated with FcR Blocking Reagent or with 10 μM Chloroquine. Individual Thai and USA plasma are indicated by numbers 1, 2, 3 and 4, 5, 6 respectively. (*) denotes an IFN-α stimulatory concentration. (B) IFN-γ induced by PHA in either PBMC alone or pretreated with FcR Blocking Reagent or Chloroquine (10 μM). Samples with no IFN-α titer are represented by a single line.
Mentions: IFN-α production promoted by Thai plasma (samples 1–3) and USA (samples 4–6) individuals were inhibited to undetectable levels in the presence of the endosomal alkalinizing agent chloroquine (Fig. 6). Additionally, IPA mediated HIV induced IFN-α production was reduced to undetectable levels when PBMCs were pre-incubated with an FcR blockade reagent containing a mixture of antibodies that block surface Fcγ receptors (Fig. 6). The combination of blocking antibodies had no effect on PBMC to produce the FcγR-independent induction of IFN-γ by phytohaemagglutinin (PHA), while chloroquine inhibited interferon induction consistent with the known dependency of interferon production on endosomal processing2526. Figure 6 is representative of three separate experiments.

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.


Related in: MedlinePlus