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C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Verani A, Scarlatti G, Comar M, Tresoldi E, Polo S, Giacca M, Lusso P, Siccardi AG, Vercelli D - J. Exp. Med. (1997)

Bottom Line: A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS.Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages.Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.

ABSTRACT
Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

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Recombinant C–C  chemokines inhibit HIV-1 replication in human MDM. MDM  from healthy donors were infected in vitro with HIV-1Ba-L  (left) or with the NSI primary viral isolate HIV-15088 (right), in  the presence or absence of LPS  (1 μg/ml) and recombinant  chemokines. Chemokines were  added to HIV-1Ba-L-infected cultures at a concentration of 250  ng/ml when used individually,  and 50 ng/ml each when used  in combination. For HIV-15088infected cultures, chemokines  were used at 10 ng/ml, individually and in combination. Supernatants from infected cultures  were harvested at different timepoints, and assayed by ELISA for  p24 Ag secretion.
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Figure 7: Recombinant C–C chemokines inhibit HIV-1 replication in human MDM. MDM from healthy donors were infected in vitro with HIV-1Ba-L (left) or with the NSI primary viral isolate HIV-15088 (right), in the presence or absence of LPS (1 μg/ml) and recombinant chemokines. Chemokines were added to HIV-1Ba-L-infected cultures at a concentration of 250 ng/ml when used individually, and 50 ng/ml each when used in combination. For HIV-15088infected cultures, chemokines were used at 10 ng/ml, individually and in combination. Supernatants from infected cultures were harvested at different timepoints, and assayed by ELISA for p24 Ag secretion.

Mentions: To assess whether C–C chemokines are sufficient to inhibit HIV-1 replication in MDM, recombinant RANTES, MIP-1α, and MIP-1β were added to HIVinfected MDM, alone or in combination. Fig. 7 (left) shows that a combination of the three chemokines, each at a concentration of 50 ng/ml, inhibited the replication of HIV-1Ba-L in infected MDM by 76%. In the same experiments, addition of LPS reduced p24 Ag release by 75%. Among the three chemokines, RANTES was the most effective one, because it inhibited HIV-1Ba-L infection as efficiently as LPS when used at a concentration of 250 ng/ml. Notably, the inhibitory effect of C–C chemokines on HIV-1 replication was even more pronounced in MDM cultures infected with NSI primary viral isolates. Indeed, Fig. 7 (right) shows that RANTES, MIP-1α, and MIP-1β blocked the replication of HIV-15088 by >75% even when used individually at a concentration as low as 10 ng/ml. The combination of the three chemokines suppressed HIV-15088 by over 90%. The concentrations of recombinant chemokines used in our experiments were physiologically significant. Indeed, the assessment of the concentrations of endogenous chemokines released by MDM during the overnight incubation with virus and LPS before washing (data not shown) demonstrated that at the time of in vitro infection, HIV is exposed to similar amounts of chemokines. These results show that recombinant chemokines are sufficient to inhibit HIV infection in human MDM.


C-C chemokines released by lipopolysaccharide (LPS)-stimulated human macrophages suppress HIV-1 infection in both macrophages and T cells.

Verani A, Scarlatti G, Comar M, Tresoldi E, Polo S, Giacca M, Lusso P, Siccardi AG, Vercelli D - J. Exp. Med. (1997)

Recombinant C–C  chemokines inhibit HIV-1 replication in human MDM. MDM  from healthy donors were infected in vitro with HIV-1Ba-L  (left) or with the NSI primary viral isolate HIV-15088 (right), in  the presence or absence of LPS  (1 μg/ml) and recombinant  chemokines. Chemokines were  added to HIV-1Ba-L-infected cultures at a concentration of 250  ng/ml when used individually,  and 50 ng/ml each when used  in combination. For HIV-15088infected cultures, chemokines  were used at 10 ng/ml, individually and in combination. Supernatants from infected cultures  were harvested at different timepoints, and assayed by ELISA for  p24 Ag secretion.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196157&req=5

Figure 7: Recombinant C–C chemokines inhibit HIV-1 replication in human MDM. MDM from healthy donors were infected in vitro with HIV-1Ba-L (left) or with the NSI primary viral isolate HIV-15088 (right), in the presence or absence of LPS (1 μg/ml) and recombinant chemokines. Chemokines were added to HIV-1Ba-L-infected cultures at a concentration of 250 ng/ml when used individually, and 50 ng/ml each when used in combination. For HIV-15088infected cultures, chemokines were used at 10 ng/ml, individually and in combination. Supernatants from infected cultures were harvested at different timepoints, and assayed by ELISA for p24 Ag secretion.
Mentions: To assess whether C–C chemokines are sufficient to inhibit HIV-1 replication in MDM, recombinant RANTES, MIP-1α, and MIP-1β were added to HIVinfected MDM, alone or in combination. Fig. 7 (left) shows that a combination of the three chemokines, each at a concentration of 50 ng/ml, inhibited the replication of HIV-1Ba-L in infected MDM by 76%. In the same experiments, addition of LPS reduced p24 Ag release by 75%. Among the three chemokines, RANTES was the most effective one, because it inhibited HIV-1Ba-L infection as efficiently as LPS when used at a concentration of 250 ng/ml. Notably, the inhibitory effect of C–C chemokines on HIV-1 replication was even more pronounced in MDM cultures infected with NSI primary viral isolates. Indeed, Fig. 7 (right) shows that RANTES, MIP-1α, and MIP-1β blocked the replication of HIV-15088 by >75% even when used individually at a concentration as low as 10 ng/ml. The combination of the three chemokines suppressed HIV-15088 by over 90%. The concentrations of recombinant chemokines used in our experiments were physiologically significant. Indeed, the assessment of the concentrations of endogenous chemokines released by MDM during the overnight incubation with virus and LPS before washing (data not shown) demonstrated that at the time of in vitro infection, HIV is exposed to similar amounts of chemokines. These results show that recombinant chemokines are sufficient to inhibit HIV infection in human MDM.

Bottom Line: A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS.Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages.Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological and Technological Research, San Raffaele Scientific Institute, Milan, Italy.

ABSTRACT
Human immunodeficiency virus-1 (HIV-1) expression in monocyte-derived macrophages (MDM) infected in vitro is known to be inhibited by lipopolysaccharide (LPS). However, the mechanisms are incompletely understood. We show here that HIV-1 suppression is mediated by soluble factors released by MDM stimulated with physiologically significant concentrations of LPS. LPS-conditioned supernatants from MDM inhibited HIV-1 replication in both MDM and T cells. Depletion of C-C chemokines (RANTES, MIP-1 alpha, and MIP-1 beta) neutralized the ability of LPS-conditioned supernatants to inhibit HIV-1 replication in MDM. A combination of recombinant C-C chemokines blocked HIV-1 infection as effectively as LPS. Here, we report an inhibitory effect of C-C chemokines on HIV replication in primary macrophages. Our results raise the possibility that monocytes may play a dual role in HIV infection: while representing a reservoir for the virus, they may contribute to the containment of the infection by releasing factors that suppress HIV replication not only in monocytes but also in T lymphocytes.

Show MeSH
Related in: MedlinePlus