Acid Sensitivity of Cell-Free and Cell-Associated HIV-1: Clinical Implications

Ongrádi, J; Ceccherini‐Nelli, Luca; Pistello, Mauro; Specter, Steven; Bendinelli, Mauro

doi:10.1089/aid.1990.6.1433

Cited by 94 publications

(60 citation statements)

References 11 publications

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“…8), and impaired HIV infectivity (47)(48)(49). The loss of HIV binding by DC-SIGN as the pH was lowered to 5.0 is consistent with previous reports which have shown that a drop in pH results in a conformational change in the DC-SIGN CRD that alters its binding capacity (50).…”

Section: Discussionsupporting

confidence: 89%

Surfactant Protein A Binds to HIV and Inhibits Direct Infection of CD4+ Cells, but Enhances Dendritic Cell-Mediated Viral Transfer

Gaiha

Dong

Palaniyar

et al. 2008

The Journal of Immunology

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The identification of surfactant protein A (SP-A) as an important innate immune factor of the lungs, amniotic fluid, and the vaginal tract suggests that it could play an important role during various stages of HIV disease progression and transmission. Therefore, we examined whether SP-A could bind to HIV and also had any effect on viral infectivity. Our data demonstrate that SP-A binds to HIV in a calcium-dependent manner that is inhibitable by mannose and EDTA. Affinity capture of the HIV viral lysate reveals that SP-A targets the envelope glycoprotein of HIV (gp120), which was confirmed by ELISA using recombinant gp120. Digestion of gp120 with endoglycosidase H abrogates the binding of SP-A, indicating that the high mannose structures on gp120 are the target of the collectin. Infectivity studies reveal that SP-A inhibits the infection of CD4+ T cells by two strains of HIV (BaL, IIIB) by >80%. Competition assays with CD4 and mAbs F105 and b12 suggest that SP-A inhibits infectivity by occlusion of the CD4-binding site. Studies with dendritic cells (DCs) demonstrate that SP-A enhances the binding of gp120 to DCs, the uptake of viral particles, and the transfer of virus from DCs to CD4+ T cells by >5-fold at a pH representative of the vaginal tract. Collectively, these results suggest that SP-A acts as a dual modulator of HIV infection by protecting CD4+ T cells from direct infection but enhancing the transfer of infection to CD4+ T cells mediated by DCs.

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Section: Discussionsupporting

confidence: 89%

Surfactant Protein A Binds to HIV and Inhibits Direct Infection of CD4+ Cells, but Enhances Dendritic Cell-Mediated Viral Transfer

Gaiha

Dong

Palaniyar

et al. 2008

The Journal of Immunology

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“…For example, excess Env could ensure more stable attachment of virions to target cells and/or be involved in receptor and/or coreceptor mediated signaling (56). In addition, excess Env may compensate for shedding or inactivation by semen (57) and cervicovaginal mucous (58). Thus, it seems likely that the increased Env content and associated enhanced infectivity of TF viruses serve to increase their transmission fitness.…”

Section: ) (B D and F)mentioning

confidence: 99%

Phenotypic properties of transmitted founder HIV-1

Parrish

Gao

Li³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

374

432

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Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.

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“…61,62 The buffering capacity of semen may help to maintain conditions that are conducive to HIV-1 stability and infection. [63][64][65][66] 72 Furthermore, complement activation in seminal fluid generates C3 cleavage and augments HIV-1 infection in epithelial cells. 73 In vaginal epithelial cells, SP induces the secretion of CCL20 and subsequent recruitment of LCs.…”

Section: 58mentioning

confidence: 99%