# Kubilay Kaan Baytunçer's File (Herpesviruses)

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# **HERPESVIRUSES**

*Wang-Shick Ryu - Molecular Virology of Human Pathogenic Viruses-Academic Press (2017)*

- Herpesviruses are found not only in human but also in many vertebrates such as mammals, birds, reptiles, and fishes. Over 130 species of herpesviruses have been reported, and they can be divided into three subgroups depending on their biological properties: alpha-, beta-, and gamma-herpesviruses.

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# **THE HUMAN HERPESVIRUSES**

**Herpes simplex viruses 1 and 2**
- Of the eight human herpesviruses, HSV-1, a prototype of human alpha-herpesvirus, will be mainly described for brevity.
- Herpes simplex virus type 1 (HSV-1) causes cold sores or oral herpes.
- HSV-1 is an enveloped virus, in which the capsid is enclosed. Some tegument proteins, such as VP16, ICP0, and Vhs, are essential for the viral infection.
- HSV-2 is related to HSV-1, exhibiting over 50% genetic similarity. HSV-2 causes disorders in the reproductive organs, such as genital herpes.
- Genital herpes, known simply as herpes, is the second most common form of herpes. Acyclovir is used for the treatment, but a vaccine is not available


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**Varicella-zoster virus**
- Varicella-zoster virus causes chicken pox to youngsters and herpes zoster to adults, which is often referred to as shingles.
- Being transmitted via an airborne route, VZV is extremely contagious, and most people are infected before or during youth.

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**Epstein-Barr virus**

- EBV (Epstein-Barr virus) is a prototype of human gamma-herpesviruses. Worldwide, over 90% of adults have already been infected by EBV. Infection with EBV occurs by oral transfer of saliva and genital secretions. EBV infects B cells of the immune system and epithelial cells.

**Human Cytomegalovirus**

- HCMV (human cytomegalovirus) is a prototype of human beta-herpesviruses. Worldwide, over 80% of adults have been infected by HCMV, as indicated by the presence of antibodies. Although they may be found throughout the body, HCMV infections are frequently associated with the salivary glands.

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# **THE VIRION AND GENOME STRUCTURE OF HSV-1**


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# **THE LIFE CYCLE OF HSV-1**

- Similar to other DNA viruses, the virus life cycle can be divided into two phases by the onset of viral genome replication: early phase and late phase. The viral genome replication occurs in the nucleus of infected cells.

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# **ATTACHMENT AND ENTRY OF HSV-1**
- HSV-1 enters cells either via direct fusion or receptor-mediated endocytosis. Virion attaches to cell surface glycosaminoglycans such as heparan sulfate for entry.

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# **TRANSCRIPTION AND TRANSLATION**

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# **GENOME REPLICATION**

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# **ASSEMBLY AND RELEASE**

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[VIDEO](https://www.youtube.com/watch?v=Dqhu0TMOXmc)

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# **LATENT INFECTION**

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# **EFFECTS ON HOST**

- Most adults are latently infected with multiple, at least two or three, herpesviruses, and are seropositive to these viral antigens. Herpesvirus infections do not cause serious diseases to healthy individuals.
- Nonetheless, the latently infected herpesviruses often cause serious sequels under certain circumstances such as in immunocompromised individuals.
- Treatment usually involves nucleoside analog antiviral drugs such as acyclovir that inhibits viral replication. Acyclovir is a prodrug, which is converted into acyclovir triphosphate that acts as an inhibitor of the viral DNA polymerase. A preventive vaccine for HSV-1 is not available.

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# **HERPESVIRUSE RESEARCHES**

- Research is currently ongoing into a variety of side-effect or co-conditions related to the herpesviruses. [These include](https://en.wikipedia.org/wiki/Herpes_simplex_research):


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**ALZHEIMER & HSV-1**

- The herpes simplex virus HSV-1 has been found in the same areas as amyloid plaques. This suggested the possibility that alzheimer disease could be treated or prevented with antiviral medication. Studies of antivirals in cell cultures have shown promising results.
- [A 2021 study](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882534/) of 265,172 subjects in Sweden over a 12 year period found that patients with herpes diagnoses not treated with antiviral drugs had a 50% increased risk of dementia over controls, but treatment with antiviral drugs reduced the incidence by 25%.

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**Development of Genome Editing Approaches against Herpes Simplex Virus Infections**
- Current anti-HSV-1 therapies effectively block viral replication and infection. However, they have little effect on viral latency and cannot completely eliminate viral infection.
- These issues, along with the emergence of drug-resistant viral strains, pose a need to develop new compounds and novel strategies for the treatment of HSV-1 infection.
- [Genome editing methods](https://www.mdpi.com/1999-4915/13/2/338/htm) represent a promising approach against viral infection by modifying or destroying the genetic material of human viruses. These editing methods include homing endonucleases (HE) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein (Cas) RNA-guided nuclease system. Recent studies have showed that both HE and CRISPR/Cas systems are effective in inhibiting HSV-1 infection in cultured cells in vitro and in mice in vivo.
[VIDEO](https://www.youtube.com/watch?v=lQaWh8VLkiU)

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> from alper: Sunumunuz, fena olmamış. Ama benim slaytlar gibi "kuru" olmuş gibi. Biraz daha güncel, ilginç içerik eklenebilir mi?

>Hocam yorumlarınız için çok teşekkür ederim. Önerileriniz doğrultusunda araştırmaya devam ettim ve HSV-1 virüsünün bağlantılı olduğu hastalıklar, yapılan araştırmalar, tedavide yeni yaklaşımlar, virüsün host üzerindeki etkileri ve tedavisi gibi başlıklar ekleyip güzel videolarla zenginleştirmeye çalıştım. Slaytın şu anki halini geliştirmek üzere yapabileceğim başka bir şey var mı hocam ?

> Epey ekleme yapmışsınız, teşekkürler. HSV proteinlerinden (capsid veya enzim olabilir) biyomühendisler içim ilham verebilecek olanlarından 1-2'si hakkında materyal bulabilirseniz eklerseniz güzel olur.

> Tamamdır hocam, bu konu hakkında biraz daha araştırma yapacağım.