HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner

Selina Poon, Carlos G. Moscoso, Onur M. Yenigun, Prasanna R. Kolatkar, R. Holland Cheng, Anders Vahlne

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: To study the dose-dependent manner of HIV-1 Tat-induced effects on viral replication, internalization and spread, and to directly observe these effects on soluble Env immunogens and virus-like particles. Design: In order to determine the manner through which Tat affects viral replication, we incubated cells, virions and soluble Env spikes with Tat at different concentrations, and directly visualized the effects of such incubation. Methods: Cell-based infectivity assays were carried out to assay Tat dose-dependency of viral infectivity. Transmission electron microscopy of virus-like particles and soluble gp140 immunogens incubated with Tat at various concentrations was performed to directly observe Tat-induced effects. Results: Treating virus with exogenous Tat increased infectivity in a dose-dependent manner. In the presence of anti-Tat antibodies, virus replication and spread were repressed, postulating Tat contributions to disease progression. When CXCR4 coreceptors were blocked, Tat treatment overcame the inhibition relative to absence of Tat treatment. Similarly, syncytium formation between chronically infected and uninfected target cells was also increased by exogenous Tat treatment. Inhibiting the CD4 receptor for virus entry abolished syncytium formation and Tat treatment was unable to overcome CD4 dependency.We show that Tat reduces virus infectivity at higher Tat concentrations through Env interactions resulting in viral aggregation. Conclusion: Treating virions or chronically infected cells with exogenous Tat could enhance virus infectivity and spread through coreceptor tropism switch or through another undetermined mechanism. The aggregation potential of Tat suggests a mechanism of negative-feedback regulation of viral replication, providing another regulative function to control viral replication.

Original languageEnglish (US)
Pages (from-to)2355-2364
Number of pages10
JournalAIDS
Volume27
Issue number15
DOIs
StatePublished - Sep 24 2013

Fingerprint

Human Immunodeficiency Virus tat Gene Products
Virion
HIV-1
Giant Cells
Viruses
Virus Internalization
CD4 Antigens
Tropism
Virus Replication
Transmission Electron Microscopy
Disease Progression
Anti-Idiotypic Antibodies

Keywords

  • Aggregation
  • HIV
  • Infectivity
  • Neutralization
  • Tat

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Poon, S., Moscoso, C. G., Yenigun, O. M., Kolatkar, P. R., Cheng, R. H., & Vahlne, A. (2013). HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner. AIDS, 27(15), 2355-2364. https://doi.org/10.1097/01.aids.0000432452.83604.59

HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner. / Poon, Selina; Moscoso, Carlos G.; Yenigun, Onur M.; Kolatkar, Prasanna R.; Cheng, R. Holland; Vahlne, Anders.

In: AIDS, Vol. 27, No. 15, 24.09.2013, p. 2355-2364.

Research output: Contribution to journalArticle

Poon, S, Moscoso, CG, Yenigun, OM, Kolatkar, PR, Cheng, RH & Vahlne, A 2013, 'HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner', AIDS, vol. 27, no. 15, pp. 2355-2364. https://doi.org/10.1097/01.aids.0000432452.83604.59
Poon, Selina ; Moscoso, Carlos G. ; Yenigun, Onur M. ; Kolatkar, Prasanna R. ; Cheng, R. Holland ; Vahlne, Anders. / HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner. In: AIDS. 2013 ; Vol. 27, No. 15. pp. 2355-2364.
@article{c418266f48ce445aaafc4061147bf241,
title = "HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner",
abstract = "Objective: To study the dose-dependent manner of HIV-1 Tat-induced effects on viral replication, internalization and spread, and to directly observe these effects on soluble Env immunogens and virus-like particles. Design: In order to determine the manner through which Tat affects viral replication, we incubated cells, virions and soluble Env spikes with Tat at different concentrations, and directly visualized the effects of such incubation. Methods: Cell-based infectivity assays were carried out to assay Tat dose-dependency of viral infectivity. Transmission electron microscopy of virus-like particles and soluble gp140 immunogens incubated with Tat at various concentrations was performed to directly observe Tat-induced effects. Results: Treating virus with exogenous Tat increased infectivity in a dose-dependent manner. In the presence of anti-Tat antibodies, virus replication and spread were repressed, postulating Tat contributions to disease progression. When CXCR4 coreceptors were blocked, Tat treatment overcame the inhibition relative to absence of Tat treatment. Similarly, syncytium formation between chronically infected and uninfected target cells was also increased by exogenous Tat treatment. Inhibiting the CD4 receptor for virus entry abolished syncytium formation and Tat treatment was unable to overcome CD4 dependency.We show that Tat reduces virus infectivity at higher Tat concentrations through Env interactions resulting in viral aggregation. Conclusion: Treating virions or chronically infected cells with exogenous Tat could enhance virus infectivity and spread through coreceptor tropism switch or through another undetermined mechanism. The aggregation potential of Tat suggests a mechanism of negative-feedback regulation of viral replication, providing another regulative function to control viral replication.",
keywords = "Aggregation, HIV, Infectivity, Neutralization, Tat",
author = "Selina Poon and Moscoso, {Carlos G.} and Yenigun, {Onur M.} and Kolatkar, {Prasanna R.} and Cheng, {R. Holland} and Anders Vahlne",
year = "2013",
month = "9",
day = "24",
doi = "10.1097/01.aids.0000432452.83604.59",
language = "English (US)",
volume = "27",
pages = "2355--2364",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "15",

}

TY - JOUR

T1 - HIV-1 Tat protein induces viral internalization through Env-mediated interactions in dose-dependent manner

AU - Poon, Selina

AU - Moscoso, Carlos G.

AU - Yenigun, Onur M.

AU - Kolatkar, Prasanna R.

AU - Cheng, R. Holland

AU - Vahlne, Anders

PY - 2013/9/24

Y1 - 2013/9/24

N2 - Objective: To study the dose-dependent manner of HIV-1 Tat-induced effects on viral replication, internalization and spread, and to directly observe these effects on soluble Env immunogens and virus-like particles. Design: In order to determine the manner through which Tat affects viral replication, we incubated cells, virions and soluble Env spikes with Tat at different concentrations, and directly visualized the effects of such incubation. Methods: Cell-based infectivity assays were carried out to assay Tat dose-dependency of viral infectivity. Transmission electron microscopy of virus-like particles and soluble gp140 immunogens incubated with Tat at various concentrations was performed to directly observe Tat-induced effects. Results: Treating virus with exogenous Tat increased infectivity in a dose-dependent manner. In the presence of anti-Tat antibodies, virus replication and spread were repressed, postulating Tat contributions to disease progression. When CXCR4 coreceptors were blocked, Tat treatment overcame the inhibition relative to absence of Tat treatment. Similarly, syncytium formation between chronically infected and uninfected target cells was also increased by exogenous Tat treatment. Inhibiting the CD4 receptor for virus entry abolished syncytium formation and Tat treatment was unable to overcome CD4 dependency.We show that Tat reduces virus infectivity at higher Tat concentrations through Env interactions resulting in viral aggregation. Conclusion: Treating virions or chronically infected cells with exogenous Tat could enhance virus infectivity and spread through coreceptor tropism switch or through another undetermined mechanism. The aggregation potential of Tat suggests a mechanism of negative-feedback regulation of viral replication, providing another regulative function to control viral replication.

AB - Objective: To study the dose-dependent manner of HIV-1 Tat-induced effects on viral replication, internalization and spread, and to directly observe these effects on soluble Env immunogens and virus-like particles. Design: In order to determine the manner through which Tat affects viral replication, we incubated cells, virions and soluble Env spikes with Tat at different concentrations, and directly visualized the effects of such incubation. Methods: Cell-based infectivity assays were carried out to assay Tat dose-dependency of viral infectivity. Transmission electron microscopy of virus-like particles and soluble gp140 immunogens incubated with Tat at various concentrations was performed to directly observe Tat-induced effects. Results: Treating virus with exogenous Tat increased infectivity in a dose-dependent manner. In the presence of anti-Tat antibodies, virus replication and spread were repressed, postulating Tat contributions to disease progression. When CXCR4 coreceptors were blocked, Tat treatment overcame the inhibition relative to absence of Tat treatment. Similarly, syncytium formation between chronically infected and uninfected target cells was also increased by exogenous Tat treatment. Inhibiting the CD4 receptor for virus entry abolished syncytium formation and Tat treatment was unable to overcome CD4 dependency.We show that Tat reduces virus infectivity at higher Tat concentrations through Env interactions resulting in viral aggregation. Conclusion: Treating virions or chronically infected cells with exogenous Tat could enhance virus infectivity and spread through coreceptor tropism switch or through another undetermined mechanism. The aggregation potential of Tat suggests a mechanism of negative-feedback regulation of viral replication, providing another regulative function to control viral replication.

KW - Aggregation

KW - HIV

KW - Infectivity

KW - Neutralization

KW - Tat

UR - http://www.scopus.com/inward/record.url?scp=84884498671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884498671&partnerID=8YFLogxK

U2 - 10.1097/01.aids.0000432452.83604.59

DO - 10.1097/01.aids.0000432452.83604.59

M3 - Article

VL - 27

SP - 2355

EP - 2364

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 15

ER -