Herpes simplex virus

Summary

Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus. As of 2016, about 67% of the world population under the age of 50 had HSV-1. In the United States, about 47.8% and 11.9% are estimated to have HSV-1 and HSV-2, respectively, though actual prevalence may be much higher. Because it can be transmitted through any intimate contact, it is one of the most common sexually transmitted infections. Symptoms Many of those who are infected never develop symptoms. Symptoms, when they occur, may include watery blisters in the skin or mucous membranes of the mouth, lips, nose, genitals, or eyes (herpes simplex keratitis). Lesions heal wit

Official source

https://en.wikipedia.org/wiki/Herpes_simplex_virus

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Related publications (19)

Adeno-associated virus (AAV) is a small non-enveloped virus and as a member of the parvovirus family, it contains a single stranded DNA genome. AAV's life cycle in vitro is strongly dependent not only on cellular factors but also on helper functions provided by other viruses, for example adenovirus, herpes virus and, to a certain extent, papillomavirus (HPV). Although AAVs are wide spread throughout the human population, no disease is yet associated with them. Accordingly, AAV became attractive as a vector for gene therapy studies, but even though the virus is well studied in vitro and now used in clinical trials as a vector, not much is known about AAV infection in vivo. AAV was initially isolated from humans together with its helper adenovirus. However, adenovirus-independent replication of AAV has been reported for a number of cellular situations, including differentiating keratinocytes with or without the presence of HPV, and in cells with an activated DNA damage response due to genotoxic agents. In the work reported here we have undertaken a systematic study of these alternative helper activities with a view to evaluating their contribution to natural infections by AAV. We used three different systems of cultured keratinocytes and showed that in each case in vitro differentiation was achieved. In two of these, the cells were from HPV-induced lesions. We found that AAV replicates efficiently in differentiating monolayer foreskin keratinocytes in the presence but not in the absence of adenovirus. Likewise naturally HPV-infected cervical keratinocytes only support the full life cycle of AAV if adenovirus is present. Even though HPV can provide certain helper functions, it is less efficient as a helper than adenovirus. We also exploited osteosarcoma cells, which are particularly well infected by AAV. Our results indicate that U2OS osteosarcoma cells are semi-permissive for AAV growth. Induction of a DNA damage response in these cells, or in HPV-containing keratinocytes, stimulates AAV genome amplification. Although AAV replication in the absence of helper virus can readily be demonstrated, this is either at a relatively low level or limited to part of the AAV growth cycle. We conclude that although these alternative helper systems can contribute to the natural history of AAV, the presence of an efficient helper virus seems likely to be needed for AAV to persist in the human population.

EPFL2009

Modified cyclodextrins as broad-spectrum antivirals

Valeria Cagno, Matteo Gasbarri, Natalia Gasilova, Matej Janecek, Samuel Thomas Jones, Francesco Stellacci

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

AMER ASSOC ADVANCEMENT SCIENCE2020

Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism

Ahmet Bekdemir, Valeria Cagno, Paulo Henrique Jacob Silva, Emma-Rose Janecek, Samuel Thomas Jones, Marie Mueller, Francesco Stellacci

Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus–cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

2018

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EPFL2009