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title: 'Muhammed Murat Cindilli **Herpesviruses** "Essential Human Virology by Jennifer Louten (2016)." Chapter 13 Pages: 235-256 link below'

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# Muhammed Murat Cindilli **Herpesviruses** "Essential Human Virology by Jennifer Louten (2016)." Chapter 13 Pages: 235-256 link below
https://www.sciencedirect.com/book/9780128009475/essential-human-virology
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# Herpesviruses
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Derived from a Greek word meaning to crawl, herpesviruses are a large dsDNA virus that causes some well-known conditions in humans such as chickenpox, cold sores, and genital herpes.

Herpesviruses are ubiquitous in nature and infect many animals, including humans. More than 100 strains of herpes virus have been described so far. Given that at least one herpes virus has been discovered in every mammalian species investigated, it is very likely that hundreds of other herpes viruses will eventually emerge. 
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# CLINICAL CONDITIONS CAUSED BY HERPESVIRUSES

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Members of the Herpesviridae family are large, enveloped viruses with an icosahedral capsid surrounding a dsDNA as shown in Table 1. Except for VZV, a respiratory virus, all other HHVs usually require close contact with infected tissues or secretions for transmission to occur due to the fragility of the virion envelope.
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<img src="https://i.imgur.com/R6rmCko.jpg" alt="drawing" width="700" height="300"/>

**Figure 1** An adult person with VZV virus


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**Table 1** Human Herpes Virusus 
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# Herpes Simplex Virus Type 1 and Type 2 (HSV-1/HHV-1 and HSV-2/HHV-2)
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HSV-1 and HSV-2 are two similar viruses that share approximately 85% homology in the protein-coding regions of their viral genomes. While HSV-1 causes 80-90% of oral herpes, most cases of genital herpes are caused by HSV-2, but either virus can infect both sites.
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<img src="https://i.imgur.com/KnZp3ZK.jpg" alt="drawing" width="250" height="250"/> <img src="https://i.imgur.com/PcwH6sF.png" alt="drawing" width="250" height="250"/>
**Figure 2** Oral and genital herpes.

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# Varicella Zoster Virus (VZV/HHV-3)
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VZV, the third member of the Alphaherpesvirinae subfamily, is officially classified as HHV-3. VZV, which generally causes chickenpox, causes an acute, productive infection followed by latent infection of sensory neurons, particularly dorsal root ganglia.
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<img src="https://i.imgur.com/QSG2rJ9.png" alt="drawing" width="" height="250"/>

**Figure 3** Varicella zoster virus (VZV) (chickenpox) rash.

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VZV is the only herpes virus that usually spreads through infected respiratory secretions. This highly contagious virus begins infection by multiplying locally in the nasopharynx and in the tonsils and regional lymph nodes after an incubation period of about 2 weeks.Primary viremia develops within a week and spreads the virus to organs such as the spleen and liver. Sensory neurons, which will later harbor the latent virus, are also infected at this time. A secondary viremia occurs and infected memory T lymphocytes circulating in tissue capillaries are thought to spread the virus to the skin and visible symptoms begin to develop.
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![](https://i.imgur.com/XaaxMtO.png)
**Figure 4** VZV latency in and reactivation from the posterior (dorsal) root ganglia.

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# Epstein–Barr Virus (EBV/HHV-4)

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Known as one of the most common human viruses in the world, EBV is officially known as HHV-4. EBV, named after the first human lymphocyte cell line, was named “EB” after the surnames of Anthony Epstein and Yvonne Barr, the researcher and laboratory technician who performed the cell culture. It is one of the childhood diseases with typical cold symptoms in children. However, in teenagers or adults, it causes 90% of cases of mononucleosis, which causes fever, severe sore throat, headaches and malaise.
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<img src="https://i.imgur.com/EZi6CyK.png" alt="drawing" width="700" height="250"/>

**Figure 5** Infectious mononucleosis (EBV).

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# Human Cytomegalovirus(CMV/HHV-5)
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Human cytomegalovirus (HCMV), a member of the Betaherpesvirinae virus subfamily, is officially known as HHV-5. It is characterized by slow replication and clinically asymptomatic infections in healthy individuals. Having the largest genome of any HHV, HCMV has many mechanisms to manipulate the infected cell and interfere with host immune responses while enabling its own replication.
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<img src="https://i.imgur.com/nMO1oiQ.png" alt="drawing" width="700" height="250"/>

**Figure 6** Cytomegalic inclusion body.

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# HHV-6A, HHV-6B, and HHV-7
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The Betaherpesvirinae subfamily includes HHV-6 and HHV-7 in addition to HCMV. These viruses have smaller genomes than HCMV. HHV-6 is divided into two separate types, HHV-6A and HHV-6B. The two viruses are approximately 95% similar, but are different viruses with different cellular tropism, antigenicity, and pathogenesis. It is difficult to use serology to distinguish between the two viruses due to the formation of cross-reactive antibodies.All three viruses infect T lymphocytes, particularly mature CD4 T cells.
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<img src="https://i.imgur.com/jW7amJV.png" alt="drawing" width="250" height="250"/><img src="https://i.imgur.com/dwxc0nB.png" alt="drawing" width="250" height="250"/>
**Figure 7** HHV-6 and HHV-7.

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# Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV-8)
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KSHV, the second human virus in the Gammaherpesvirinae subfamily, officially known as HHV-8, was the last HHV discovered in 1994. Like EBV, the virus infects B lymphocytes and becomes latent. Unlike other herpes viruses, KSHV seroprevalence varies considerably depending on the region of the world. The virus is most commonly spread through homosexual activity, but heterosexual activity can also transmit the virus. There is a much higher amount of virus in saliva than in genital secretions or semen.
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<img src="https://i.imgur.com/pJPsr2P.png" alt="drawing" width="500" height="250"/>

**Figure 8** A relapsing inflammatory syndrome and active human HHV-8 infection

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# MOLECULAR VIROLOGY
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The nine human viruses of the Herpesviridae family are divided into three subfamilies, Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae, based on their growth characteristics and delay targets. These viruses are all large, complex T=16 viruses with a ∼100nm icosahedral capsid of 150 hexons and 12 pentons for a total of 162 capsomeres. The capsid, which consists of four major proteins and several minor proteins, assembles in the nucleus and is surrounded by an amorphous mass of 15-40 different proteins called the tegument
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<img src="https://i.imgur.com/zA8Hsgx.png" alt="drawing" width="" height="250"/>

**Figure 9** Herpesvirus virion structure.

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HHV shares homology among 40 essential proteins required throughout the replication process, including five envelope proteins and several enzymes and proteins involved in DNA replication. Their genomes also encode a set of proteins that mimic host proteins and interfere in a complex way with the immune response to viruses.
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![](https://i.imgur.com/awZEDCb.jpg)

**Figure 10** Electron micrograph view of various viruses from the Herpesviridae family.

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# Attachment, Penetration, and Uncoating
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Herpesviruses have many different glycoproteins embedded in their envelope, higher than 11 for HSV-1 and HSV-2. A total of about 659 protein projections extend from the surface of each virion. Unlike other viruses, such as influenza, which have a single glycoprotein that mediates both attachment and fusion, a subset of herpes virus glycoproteins is involved in the process. First, glycoprotein B (gB) and gC reversibly bind to glycosaminoglycans (GAGs) extending from the cell surface, including heparan sulfate and chondroitin sulfate. We can see entry of herpesvirus in Figure 10 clearly.
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<img src="https://i.imgur.com/hbUDM5U.jpg" alt="drawing" width="600" height="500"/>

**Figure 10** Herpesvirus entry

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