Idée - Virology - # SIV Glycosylation Differences

Comparing SIV Glycosylation, Infectivity, and Neutralization Sensitivity

Q: How do host cell-dependent glycosylation differences impact HIV transmission dynamics?

Host cell-dependent glycosylation differences can significantly impact HIV transmission dynamics by influencing viral infectivity, neutralization sensitivity, and interactions with immune cells. In the context of the study using SIV as a model for HIV, it was observed that viruses produced in macrophages (M-SIV) exhibited distinct glycosylation patterns compared to those produced in CD4+ T cells (T-SIV). These differences in glycan composition affected various aspects of viral behavior. Infectivity: M-SIV demonstrated higher infectivity than T-SIV, even when accounting for Env incorporation levels. This suggests that the specific glycan structures present on gp120 influenced the ability of the virus to enter and replicate within target cells efficiently. Viral Spread: The study showed that M-SIV was more effectively disseminated by lectins like DC-SIGN compared to T-SIV. This indicates that host cell-specific glycans could influence how viruses interact with immune cells and potentially enhance their spread within the body. Neutralization Sensitivity: Differences in glycan profiles between M-SIV and T-SIV also impacted their susceptibility to carbohydrate binding agents (CBAs) and neutralizing antibodies. For example, T-SIV with higher oligomannose content was more sensitive to mannose-specific CBAs, while M-SIV was better neutralized by sera from infected animals. Overall, these findings suggest that host cell-dependent glycosylation variations play a crucial role in shaping viral characteristics related to transmission dynamics such as infectivity, spread efficiency, and vulnerability to interventions targeting viral proteins.

Q: How might host cell-specific glycosylation affect the selection of candidate therapeutics for HIV prevention?

Host cell-specific glycosylation can have implications for selecting candidate therapeutics aimed at preventing HIV infection or controlling its spread through various mechanisms: Antibody Therapies: The study highlighted how differences in Env glycosylation between viruses produced in macrophages versus CD4+ T cells influenced their sensitivity to neutralizing antibodies derived from infected animals. Understanding these variations is essential when designing antibody-based therapies targeting specific epitopes on Env. Carbohydrate Binding Agents (CBAs): Host cell-derived features of SIV were shown to define susceptibility towards CBAs like mannose-specific lectins which could inhibit virus infection. The differential response of viruses based on their origin provides insights into how CBAs may be utilized as potential therapeutic agents against different strains or variants. Therapeutic Development Strategies: Considering the impact of host-cell dependent traits on viral behavior and responses to interventions like antibodies or lectins can guide researchers in developing tailored therapeutic strategies based on understanding how specific virus populations interact with different components of the immune system.

Concepts de base

The author explores the impact of host cell-dependent glycosylation differences on SIV infectivity and neutralization sensitivity, highlighting the importance of these factors in shaping viral characteristics.

Résumé

The study delves into the glycosylation variations between SIV produced in CD4+ T cells and macrophages. Results show that T-SIV has higher levels of oligomannose-type N-glycans compared to M-SIV. Additionally, M-SIV exhibits greater infectivity and is more efficiently transmitted by lectins than T-SIV. The glycan profiles of both viruses differ significantly, with M-SIV displaying more complex glycans. These differences influence susceptibility to carbohydrate binding agents (CBAs) and neutralizing antibodies, with T-SIV being more sensitive to mannose-specific CBAs while M-SIV is better neutralized by sera. The findings suggest that host cell-dependent glycosylation plays a crucial role in determining viral characteristics and response to interventions.

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biorxiv.org

Stats

Pooled viral supernatants from CD4+ T cells contained 6.5-fold more p27-capsid antigen per ml on average than viral supernatants from macrophages.
T-SIV exhibited increased relative levels of oligomannose structures on gp120 compared to M-SIV.
M-SIV gp120 displayed more extensive branching of complex glycans compared to T-SIV.
A noteworthy 62% reduction in Env incorporation was observed for T-SIV when compared to M-SIV.

Citations

"The producer cell type can influence virus characteristics important for viral spread."
"Differences originating from the virus-producing cell can influence the efficacy of CBA and antibody neutralization."

Idées clés tirées de

Macrophage- and CD4+ T cell-derived SIV differ in glycosylation, infectivity and neutralization sensitivity

by Karsten,C. B... à www.biorxiv.org 01-02-2024

https://www.biorxiv.org/content/10.1101/2024.01.02.572735v1

Questions plus approfondies

How do host cell-dependent glycosylation differences impact HIV transmission dynamics?

Host cell-dependent glycosylation differences can significantly impact HIV transmission dynamics by influencing viral infectivity, neutralization sensitivity, and interactions with immune cells. In the context of the study using SIV as a model for HIV, it was observed that viruses produced in macrophages (M-SIV) exhibited distinct glycosylation patterns compared to those produced in CD4+ T cells (T-SIV). These differences in glycan composition affected various aspects of viral behavior.

Infectivity: M-SIV demonstrated higher infectivity than T-SIV, even when accounting for Env incorporation levels. This suggests that the specific glycan structures present on gp120 influenced the ability of the virus to enter and replicate within target cells efficiently.

Viral Spread: The study showed that M-SIV was more effectively disseminated by lectins like DC-SIGN compared to T-SIV. This indicates that host cell-specific glycans could influence how viruses interact with immune cells and potentially enhance their spread within the body.

Neutralization Sensitivity: Differences in glycan profiles between M-SIV and T-SIV also impacted their susceptibility to carbohydrate binding agents (CBAs) and neutralizing antibodies. For example, T-SIV with higher oligomannose content was more sensitive to mannose-specific CBAs, while M-SIV was better neutralized by sera from infected animals.

Overall, these findings suggest that host cell-dependent glycosylation variations play a crucial role in shaping viral characteristics related to transmission dynamics such as infectivity, spread efficiency, and vulnerability to interventions targeting viral proteins.

How might host cell-specific glycosylation affect the selection of candidate therapeutics for HIV prevention?

Host cell-specific glycosylation can have implications for selecting candidate therapeutics aimed at preventing HIV infection or controlling its spread through various mechanisms:

Antibody Therapies: The study highlighted how differences in Env glycosylation between viruses produced in macrophages versus CD4+ T cells influenced their sensitivity to neutralizing antibodies derived from infected animals. Understanding these variations is essential when designing antibody-based therapies targeting specific epitopes on Env.

Carbohydrate Binding Agents (CBAs): Host cell-derived features of SIV were shown to define susceptibility towards CBAs like mannose-specific lectins which could inhibit virus infection. The differential response of viruses based on their origin provides insights into how CBAs may be utilized as potential therapeutic agents against different strains or variants.

Therapeutic Development Strategies: Considering the impact of host-cell dependent traits on viral behavior and responses to interventions like antibodies or lectins can guide researchers in developing tailored therapeutic strategies based on understanding how specific virus populations interact with different components of the immune system.