scholarly journals Agmatine-Containing Poly(amidoamine)s as a Novel Class of Antiviral Macromolecules: Structural Properties andIn VitroEvaluation of Infectivity Inhibition

2014 ◽  
Vol 58 (10) ◽  
pp. 6315-6319 ◽  
Author(s):  
Manuela Donalisio ◽  
Elisabetta Ranucci ◽  
Valeria Cagno ◽  
Andrea Civra ◽  
Amedea Manfredi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Vesicular Stomatitis Virus ◽  
Human Papillomavirus 16 ◽  
Human Rotavirus ◽  
Vesicular Stomatitis ◽  
Syncytial Virus ◽  
Simplex Virus ◽  
Structural Versatility

ABSTRACTPoly(amidoamine)s (PAAs) are multifunctionaltert-amine polymers endowed with high structural versatility. Here we report on the screening of a minilibrary of PAAs against a panel of viruses. The PAA AGMA1 showed antiviral activity against herpes simplex virus, human cytomegalovirus, human papillomavirus 16, and respiratory syncytial virus but not against human rotavirus and vesicular stomatitis virus. The results suggest the contribution of both a polycationic nature and side guanidine groups in imparting antiviral activity.

scholarly journals Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Ezequiel Dantas ◽  
Fernando Erra Díaz ◽  
Pehuén Pereyra Gerber ◽  
Augusto Varese ◽  
Diana Alicia Jerusalinsky ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Respiratory Syncytial Virus ◽  
Herpes Simplex ◽  
Low Ph ◽  
Vaginal Mucosa ◽  
Ph Values ◽  
Syncytial Virus ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Hiv 1

ABSTRACTHistidine-rich glycoprotein (HRG) is an abundant plasma protein with a multidomain structure, allowing its interaction with many ligands, including phospholipids, plasminogen, fibrinogen, IgG antibodies, and heparan sulfate. HRG has been shown to regulate different biological responses, such as angiogenesis, coagulation, and fibrinolysis. Here, we found that HRG almost completely abrogated the infection of Ghost cells, Jurkat cells, CD4+T cells, and macrophages by HIV-1 at a low pH (range, 6.5 to 5.5) but not at a neutral pH. HRG was shown to interact with the heparan sulfate expressed by target cells, inhibiting an early postbinding step associated with HIV-1 infection. More importantly, by acting on the viral particle itself, HRG induced a deleterious effect, which reduces viral infectivity. Because cervicovaginal secretions in healthy women show low pH values, even after semen deposition, our observations suggest that HRG might represent a constitutive defense mechanism in the vaginal mucosa. Of note, low pH also enabled HRG to inhibit the infection of HEp-2 cells and Vero cells by respiratory syncytial virus (RSV) and herpes simplex virus 2 (HSV-2), respectively, suggesting that HRG might display broad antiviral activity under acidic conditions.IMPORTANCEVaginal intercourse represents a high-risk route for HIV-1 transmission. The efficiency of male-to-female HIV-1 transmission has been estimated to be 1 in every 1,000 episodes of sexual intercourse, reflecting the high degree of protection conferred by the genital mucosa. However, the contribution of different host factors to the protection against HIV-1 at mucosal surfaces remains poorly defined. Here, we report for the first time that acidic values of pH enable the plasma protein histidine-rich glycoprotein (HRG) to strongly inhibit HIV-1 infection. Because cervicovaginal secretions usually show low pH values, our observations suggest that HRG might represent a constitutive antiviral mechanism in the vaginal mucosa. Interestingly, infection by other viruses, such as respiratory syncytial virus and herpes simplex virus 2, was also markedly inhibited by HRG at low pH values, suggesting that extracellular acidosis enables HRG to display broad antiviral activity.

scholarly journals Valosin-Containing Protein (VCP/p97) Is a Potential Antiviral Target against Mononegavirales

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 108
Author(s):  
Victor Latorre ◽  
Ron Geller
Keyword(s):  
Life Cycle ◽  
Respiratory Syncytial Virus ◽  
Vesicular Stomatitis Virus ◽  
Molecular Chaperones ◽  
Cellular Machinery ◽  
Vesicular Stomatitis ◽  
Medical Importance ◽  
Syncytial Virus ◽  
Chaperone Network

The viral order Mononegavirales consist of eight virus families. Members of these families include some of the most infectious (Measles, lethal (Ebola and Rabies), and most common viruses (Respiratory syncytial virus, RSV). Despite their medical importance, few vaccines and no antiviral treatments are available for treating infections with these viruses. Being obligate cellular parasites, viruses must rely on the cellular machinery for their replication. One example of this is the widespread use of molecular chaperones, which assist the correct folding of newly synthesized proteins, refold misfolded or aggregated proteins, and play key roles in maintaining proteostasis in cells. Targeting chaperones required for viral replication may, therefore, provide an antiviral approach. In this work, we set out to identify all the members of the cytoplasmic chaperone network that are involved in the replication of RSV using an RNA interference screen. Among our hits is valosin-containing protein (VCP; also known as p97), a chaperone involved in ubiquitin-mediated protein degradation, which has been shown to play a role in the life cycle of several viruses. We investigated the role of VCP during RSV and vesicular stomatitis virus (VSV) infections using specific VCP inhibitors. Our results suggest that VCP activity is necessary for RSV and VSV replication and may constitute a promising antiviral approach for the Mononegavirales.

scholarly journals Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4+ Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

2006 ◽  
Vol 80 (9) ◽  
pp. 4447-4457 ◽  
Author(s):  
Robert J. Natuk ◽  
David Cooper ◽  
Min Guo ◽  
Priscilla Calderon ◽  
Kevin J. Wright ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Immune Responses ◽  
Vesicular Stomatitis Virus ◽  
Guinea Pigs ◽  
Wild Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Vesicular Stomatitis ◽  
Simplex Virus

ABSTRACT Recombinant vesicular stomatitis virus (rVSV) vectors offer an attractive approach for the induction of robust cellular and humoral immune responses directed against human pathogen target antigens. We evaluated rVSV vectors expressing full-length glycoprotein D (gD) from herpes simplex virus type 2 (HSV-2) in mice and guinea pigs for immunogenicity and protective efficacy against genital challenge with wild-type HSV-2. Robust Th1-polarized anti-gD immune responses were demonstrated in the murine model as measured by induction of gD-specific cytotoxic T lymphocytes and increased gamma interferon expression. The isotype makeup of the serum anti-gD immunoglobulin G (IgG) response was consistent with the presence of a Th1-CD4+ anti-gD response, characterized by a high IgG2a/IgG1 IgG subclass ratio. Functional anti-HSV-2 neutralizing serum antibody responses were readily demonstrated in both guinea pigs and mice that had been immunized with rVSV-gD vaccines. Furthermore, guinea pigs and mice were prophylactically protected from genital challenge with high doses of wild-type HSV-2. In addition, guinea pigs were highly protected against the establishment of latent infection as evidenced by low or absent HSV-2 genome copies in dorsal root ganglia after virus challenge. In summary, rVSV-gD vectors were successfully used to elicit potent anti-gD Th1-like cellular and humoral immune responses that were protective against HSV-2 disease in guinea pigs and mice.

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