Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation.

In the present study, we demonstrated that expression of the LFA-1 molecule is necessary for cell fusion and syncytia formation in human immunodeficiency virus (HIV)-infected CD4+ T lymphocytes. In contrast, the lack of expression of LFA-1 does not influence significantly cell-to-cell transmission of HIV. In fact, LFA-1- T lymphocytes obtained from a leukocyte adhesion deficiency patient were unable to fuse and form syncytia when infected with HIV-1 or HIV-2, despite the fact that efficiency of HIV infection (i.e., virus entry, HIV spreading, and levels of virus replication) was comparable with that observed in LFA-1+ T lymphocytes. In addition, we provide evidence that LFA-1 by mediating cell fusion contributes to the depletion of HIV-infected CD4+ T lymphocytes in vitro.

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In vitro antiviral activities of sulfated polysaccharides from a marine microalga (Cochlodinium polykrikoides) against human immunodeficiency virus and other enveloped viruses

International Journal of Biological Macromolecules ◽

10.1016/0141-8130(95)98157-t ◽

1995 ◽

Vol 17 (5) ◽

pp. 293-297 ◽

Cited By ~ 82

Author(s):

Masahiko Hasui ◽

Masahiro Matsuda ◽

Koichi Okutani ◽

Shiro Shigeta

Keyword(s):

Human Immunodeficiency Virus ◽

Sulfated Polysaccharides ◽

Cochlodinium Polykrikoides ◽

Enveloped Viruses ◽

Marine Microalga ◽

Immunodeficiency Virus ◽

Antiviral Activities

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Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding.

Journal of Experimental Medicine ◽

10.1084/jem.172.4.1143 ◽

1990 ◽

Vol 172 (4) ◽

pp. 1143-1150 ◽

Cited By ~ 38

Author(s):

F Celada ◽

C Cambiaggi ◽

J Maccari ◽

S Burastero ◽

T Gregory ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Monoclonal Antibodies ◽

Cell Surface ◽

Membrane Fusion ◽

Humoral Response ◽

Gp120 Binding ◽

Binding Event ◽

Immunodeficiency Virus ◽

Syncytia Formation ◽

Soluble Cd4

We studied the humoral response of mice immunized with soluble CD4-rgp120 complex, testing polyclonal and monoclonal antibodies (mAbs) with the aim of identifying molecular changes that take place after the first interaction between human immunodeficiency virus and the cell surface. The antisera had a paradoxically high syncytia-blocking titer associated with anti-CD4 specificity, while their capacity to inhibit CD4-gp120 binding was relatively modest. One of the mAbs produced from these responders blocks syncytia formation but does not inhibit CD4 interaction with gp120. Apparently, this mAb interacts with the CD4 moiety of CD4-gp120 complex and prevents a post-binding event necessary for membrane fusion and viral infection.

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Potent and Selective Activity against Human Immunodeficiency Virus 1 (HIV-1) of Thymelaea hirsuta Extracts

Viruses ◽

10.3390/v12060664 ◽

2020 ◽

Vol 12 (6) ◽

pp. 664

Author(s):

Giuseppina Sanna ◽

Silvia Madeddu ◽

Giuseppe Murgia ◽

Gabriele Serreli ◽

Michela Begala ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

New Drugs ◽

Early Event ◽

Virus Infectivity ◽

Low Concentration ◽

Immunodeficiency Virus ◽

Thymelaea Hirsuta ◽

Syncytia Formation ◽

Hiv 1 ◽

Selective Activity

Historically, natural products have been the most successful source of inspiration for the development of new drugs. Members of the Thymelaeaceae family have been of interest owing to their excellent medicinal value. Given the successful history of natural product-based drug discovery, extracts from the aerial parts of Thymelaea hirsuta were evaluated for their potential anti-human immunodeficiency virus type 1 (HIV-1) activity. Ethyl acetate extracts from leaves (71B) and branches (72B) of Thymelaea hirsuta showed potent and selective activity against HIV-1 wt (EC50 = 0.8 µg/mL) at non-cytotoxic concentrations (CC50 > 100 µg/mL). They proved to be active against HIV-1 variants carrying clinically relevant NNRTI and NRTI mutations at low concentration (0.3–4 µg/mL range) and against the M-tropic strain HIV-1 BaL. The 72B extract, chosen as a lead, was not able to inhibit the RT and protease enzymatic functions. Furthermore, it was not virucidal, since exposure of HIV to high concentration did not affect virus infectivity. The pre-clinical safety profile of this extract showed no adverse effect on the growth of Lactobacilli, and non-toxic concentration of the extract did not influence the Caco-2 epithelial cells monolayer integrity. Additionally, extract 72B prevented syncytia formation at low concentration (0.4 µg/mL). The potent inhibitory effect on the syncytia formation in co-cultures showed that 72B inhibits an early event in the replication cycle of HIV. All of these findings prompt us to carry on new studies on Thymelaea hirsuta extracts.

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Histone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection

Molecular Biology of the Cell ◽

10.1091/mbc.e05-04-0354 ◽

2005 ◽

Vol 16 (11) ◽

pp. 5445-5454 ◽

Cited By ~ 82

Author(s):

Agustín Valenzuela-Fernández ◽

Susana Álvarez ◽

Mónica Gordon-Alonso ◽

Marta Barrero ◽

Ángeles Ursa ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Cell Fusion ◽

Membrane Dynamics ◽

Fusion Pore ◽

Dependent Manner ◽

Histone Deacetylase 6 ◽

Surface Receptors ◽

Immunodeficiency Virus ◽

Syncytia Formation ◽

Hiv 1

Efficient human immunodeficiency virus (HIV)-1 infection depends on multiple interactions between the viral gp41/gp120 envelope (Env) proteins and cell surface receptors. However, cytoskeleton-associated proteins that modify membrane dynamics may also regulate the formation of the HIV-mediated fusion pore and hence viral infection. Because the effects of HDAC6-tubulin deacetylase on cortical α-tubulin regulate cell migration and immune synapse organization, we explored the possible role of HDAC6 in HIV-1-envelope-mediated cell fusion and infection. The binding of the gp120 protein to CD4+-permissive cells increased the level of acetylated α-tubulin in a CD4-dependent manner. Furthermore, overexpression of active HDAC6 inhibited the acetylation of α-tubulin, and remarkably, prevented HIV-1 envelope-dependent cell fusion and infection without affecting the expression and codistribution of HIV-1 receptors. In contrast, knockdown of HDAC6 expression or inhibition of its tubulin deacetylase activity strongly enhanced HIV-1 infection and syncytia formation. These results demonstrate that HDAC6 plays a significant role in regulating HIV-1 infection and Env-mediated syncytia formation.

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Activity of a Sulfated Polysaccharide Extracted from the Red Seaweed Aghardhiella Tenera against Human Immunodeficiency Virus and Other Enveloped Viruses

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029400500503 ◽

1994 ◽

Vol 5 (5) ◽

pp. 297-303 ◽

Cited By ~ 61

Author(s):

M. Witvrouw ◽

J. A. Este ◽

M. Q. Mateu ◽

D. Reymen ◽

G. Andrei ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Dextran Sulfate ◽

Cytopathic Effect ◽

Syncytium Formation ◽

Sulfated Polysaccharide ◽

Red Seaweed ◽

Enveloped Viruses ◽

Immunodeficiency Virus ◽

Spectrum Activity ◽

Hiv 1

A galactan sulfate (GS) was isolated from an aqueous extract of the red seaweed Aghardhiella tenera and partially purified. GS inhibited the cytopathic effect of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in MT-4 cells at concentrations 10-fold higher than those required for the inhibition by dextran sulfate (MW 5000) of the cytopathic effect of HIV-1 and HIV-2 (50% inhibitory concentrations: 0.5 and 0.05 μg ml−1, respectively). GS suppressed syncytium formation between MOLT-4 cells and persistently HIV-1- or HIV-2-infected HUT-78 cells at concentrations higher than 5 μg ml−1. Like dextran sulfate (DS) and aurintricarboxylic acid (ATA), GS inhibited the binding of HIV-1 to the cells and the binding of anti-gp120 mAb to HIV-1 gp120. Like DS and ATA, GS proved active not only against HIV-1 and HIV-2 but also against other enveloped viruses, i.e. herpes-, toga-, arena-, myxo- and rhabdoviruses. GS represents a natural polysaccharide with broad-spectrum activity against a number of important viral pathogens.

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