High-Multiplicity HIV-1 Infection and Neutralizing Antibody Evasion Mediated by the Macrophage-T Cell Virological Synapse

Duncan, Christopher J A; Williams, James P.; Schiffner, Torben; Gärtner, Kathleen; Ochsenbauer, Christina; Kappes, John C.; Russell, Rebecca A.; Frater, John; Sattentau, Quentin J.

doi:10.1128/jvi.03245-13

Cited by 100 publications

(115 citation statements)

References 62 publications

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“…A similar inhibition was previously observed between cellfree and HIV-1 transfer from MoDC to CD4 T cells (31) and confirmed in this study. Interestingly, a similar inhibitory activity of VRC01 was recently reported for the HIV-1 transmission from macrophages to T cells (43). In contrast, Abela et al and Sagar et al found that VRC01 did not block cell-mediated HIV-1 transmission from HIV-1-infected PBMC or mature MoDC to TZM-bl target cells and proposed that cell-to-cell transmission enabled HIV-1 to evade inhibition by anti-gp120 Ab (44,45).…”

mentioning

confidence: 86%

Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

Lederle

Laumond

et al. 2014

J Virol

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mentioning

confidence: 86%

Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

Lederle

Laumond

et al. 2014

J Virol

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“…Whether the MOIs in a leaf follow a multimodal distribution in other plant viruses could be tested using a combination of in situ approaches, as we did in this work. Beyond plant viruses, current data on HIV also suggest a multimodal distribution of the MOIs depending on the infection route, with a low MOI when the infection takes place from cell-free virus and a high MOI during cell-to-cell virus transfers (48).…”

Section: Discussionmentioning

confidence: 99%

The Multiplicity of Cellular Infection Changes Depending on the Route of Cell Infection in a Plant Virus

Gutiérrez

Pirolles

Yvon

et al. 2015

J Virol

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The multiplicity of cellular infection (MOI) is the number of virus genomes of a given virus species that infect individual cells. This parameter chiefly impacts the severity of within-host population bottlenecks as well as the intensity of genetic exchange, competition, and complementation among viral genotypes. Only a few formal estimations of the MOI currently are available, and most theoretical reports have considered this parameter as constant within the infected host. Nevertheless, the colonization of a multicellular host is a complex process during which the MOI may dramatically change in different organs and at different stages of the infection. IMPORTANCEThe MOI is the size of the viral population colonizing cells and defines major phenomena in virus evolution, like the intensity of genetic exchange and the size of within-host population bottlenecks. However, few studies have quantified the MOI, and most consider this parameter as constant during infection. Our results reveal that the MOI can depend largely on the route of cell infection in a systemically infected leaf. The MOI is usually one genome per cell when cells are infected from virus particles moving long distances in the vasculature, whereas it is much higher during subsequent cell-to-cell movement in mesophyll. However, a fast-acting superinfection exclusion prevents cell coinfection by merging populations originating from different primary foci within a leaf. This complex colonization pattern results in a situation where within-cell interactions are occurring almost exclusively among kin and explains the common but uncharacterized phenomenon of genotype spatial segregation in infected plants.V iral populations can evolve rapidly, even during a single host infection, and the resulting changes in the population ultimately can affect the outcome of viral diseases. A clear example of this is the emergence of drug-resistant mutants of animal/human viruses, of resistance-breaking variants of plant viruses, or of recombinant genotypes with an enlarged host range. Therefore, it is not surprising that increasing efforts are being made to characterize parameters defining within-host evolution of viral populations.Since viruses are obligate intracellular parasites, a fundamental parameter determining their within-host population dynamics/ genetics is the multiplicity of cellular infection (MOI), defined as the number of genomes of a given virus species that infects a cell. The MOI influences two major processes in viral evolution, namely, the population bottlenecks and the interactions among genotypes. Within-host bottlenecks are linked to the number of infected cells during host colonization and to the MOI at which these cells are infected. The overall intensity of interactions among viral genomes, i.e., competition, genetic exchange, functional complementation, and collective action, depends to a large extent on the probability of encountering different genotypes within host cells, a probability that is directly linked to the MOI. Given the ...

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“…Several different techniques have been used to distinguish target cells from effector cells, such as labeling of cells with fluorescent dyes (21) or mechanical separation of cells by the use of transwells or by continuous shaking of mixed cells (31). However, each of these approaches has its issues.…”

Section: Discussionmentioning

confidence: 99%

Improvement of HIV-1 and Human T Cell Lymphotropic Virus Type 1 Replication-Dependent Vectors via Optimization of Reporter Gene Reconstitution and Modification with Intronic Short Hairpin RNA

Shunaeva

Potashnikova

Пичугин

et al. 2015

J Virol

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Cell-to-cell transmission is an efficient mechanism to disseminate human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic virus type 1 (HTLV-1). However, it has been challenging to quantify the level of cell-to-cell transmission because the virus-producing cells cannot be easily distinguished from infected target cells. We have previously described replication-dependent vectors that can quantify infection events in cocultured cells. These vectors contain an antisense-oriented promoter and reporter gene interrupted by a sense-oriented intron from the human gamma-globin gene. This strategy prevents expression of the reporter gene in the transfected cells but permits its expression in target cells after infection. However, the gamma-globin intron is not efficiently removed by splicing in the aforementioned vectors, thereby reducing the level of reporter gene expression after transduction into target cells. Here, we used two approaches to improve the replication-dependent vectors. First, we improved the splicing events that remove the gamma-globin intron by optimizing the intron insertion site within the reporter gene. Second, we improved the packaging of the spliced RNA without the gamma-globin intron by targeting the introncontaining RNA via microRNA 30 (miR30)-based short hairpin RNAs. Using two optimized fluorescent reporter vectors and flow cytometry, we determined that multiply HIV-1-infected cells were generated at a higher frequency in coculture than in cellfree infection; furthermore, this increase was dependent upon viruses bearing HIV-1 Env. Compared with previously described vectors, these improved vectors can quantify the infection in lymphocytes and in primary cells with a higher sensitivity and allow the detection and quantitation of multiply infected cells, providing better tools to study retroviral cell-mediated infection. IMPORTANCEThe human-pathogenic retroviruses HTLV-1 and HIV-1 can be transmitted more efficiently in vivo via direct contact of infected cells with healthy target cells than through cell-free virion-mediated infection. Despite its importance, cell-to-cell transmission has been difficult to quantify because the previously infected cells and the newly infected cells are mixed together in the same culture. In the current study, we generated vectors that are significantly improved over the previously described replication-dependent vectors. As a result, these improved vectors can efficiently detect and quantify cell-to-cell transmission or new infection events in cells in mixed culture. These luciferase-or fluorescence protein-based reporter vectors can be used to quantify and study HIV-1 or HTLV-1 cell-mediated infection in a simple one-step transfection/infection assay.

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High-Multiplicity HIV-1 Infection and Neutralizing Antibody Evasion Mediated by the Macrophage-T Cell Virological Synapse

Abstract: Macrophage infection is considered to play an important role in HIV-

Cited by 100 publications

References 62 publications

Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

The Multiplicity of Cellular Infection Changes Depending on the Route of Cell Infection in a Plant Virus

Improvement of HIV-1 and Human T Cell Lymphotropic Virus Type 1 Replication-Dependent Vectors via Optimization of Reporter Gene Reconstitution and Modification with Intronic Short Hairpin RNA

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