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group_2_presentation_3_-_herpes_simplex_virus [2018/03/30 19:43] yousifcr |
group_2_presentation_3_-_herpes_simplex_virus [2018/03/30 19:59] (current) babadim [Transmission of HSV-1] |
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| ====== Herpes Simplex Virus ====== | ====== Herpes Simplex Virus ====== | ||
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| ====== Transmission of HSV-1 ====== | ====== Transmission of HSV-1 ====== | ||
| - | <box 20% round right| >{{ :herpes.jpg?200|}}</box|Figure 4: An individual exhibiting a cold sore caused by HSV-1. (IN TEXT)> | + | <box 20% round right| >{{ :herpes.jpg?200|}}</box|Figure 4: An individual exhibiting a cold sore caused by HSV-1. https://skinpractice.com/best-product-reviews-for-cold-sores/> |
| - | Initial infection with HSV1 is caused by contact with mucosal surfaces or abraded skin (Whitley & Roizman, 2001) in regions such as the lips, mouth, and skin above the waist (Nahmias, Keyserling & Lee, 1989). An individual can be affected with HSV-1 through close nonsexual contact with an affected individual such as kissing (even on the cheek), sharing utensils and sharing drinks, as the virus can remain viable for a brief period of time on skin, clothing and plastics (Fatahzadeh & Schwartz, 2007). An individual is most contagious when they are exhibiting cold sores or lesions, but is still contagious without showing symptoms. | + | Initial infection with HSV-1 is caused by contact with mucosal surfaces or abraded skin (Whitley & Roizman, 2001) in regions such as the lips, mouth, and skin above the waist (Nahmias, Keyserling & Lee, 1989). An individual can be affected with HSV-1 through close nonsexual contact with an affected individual such as kissing (even on the cheek), sharing utensils and sharing drinks, as the virus can remain viable for a brief period of time on skin, clothing and plastics (Fatahzadeh & Schwartz, 2007). An individual is most contagious when they are exhibiting cold sores or lesions, but is still contagious without showing symptoms. |
| HSV-1 invades surfaces through the interaction of cell surface receptors with viral glycoproteins (Heldwein & Krummenacher, 2008). Nectin-1 is a cell adhesion molecule and HVEM is the herpes virus entry mediator that is found on the surface of different cells (Shui & Kronenberg, 2013). Nectin-1 is found on oral epithelium cells and HVEM is expressed in approximately 40% of cells. One or both of these receptors bind with viral glycoproteins, with glycoprotein D being the principle glycoprotein. The virus then invades the epithelium through the basal layer (Thier et al., 2017). | HSV-1 invades surfaces through the interaction of cell surface receptors with viral glycoproteins (Heldwein & Krummenacher, 2008). Nectin-1 is a cell adhesion molecule and HVEM is the herpes virus entry mediator that is found on the surface of different cells (Shui & Kronenberg, 2013). Nectin-1 is found on oral epithelium cells and HVEM is expressed in approximately 40% of cells. One or both of these receptors bind with viral glycoproteins, with glycoprotein D being the principle glycoprotein. The virus then invades the epithelium through the basal layer (Thier et al., 2017). | ||
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| - | The current model for membrane fusion between HSV and the host cell suggests that binding to one of the gD receptors using Nectin-1 (both HSV1 and HSV2) and Nectin-2 (HSV2) induces a conformational change in gD that initiates the fusion between the virus and the host cell. The conformational change activates a multi-glycoprotein complex involving gB, gD, gH, and gL receptors. Once the viral envelope is fused with the cellular membrane, viral and cellular membranes are merged and lipid mixing occurs. This results in the release of the viral nucleocapsid and tegument proteins into the host cell’s cytoplasm. The gB receptor is primarily responsible for this (Figure 8) | + | The current model for membrane fusion between HSV and the host cell suggests that binding to one of the gD receptors using Nectin-1 (both HSV-1 and HSV-2) and Nectin-2 (HSV-2) induces a conformational change in gD that initiates the fusion between the virus and the host cell. The conformational change activates a multi-glycoprotein complex involving gB, gD, gH, and gL receptors. Once the viral envelope is fused with the cellular membrane, viral and cellular membranes are merged and lipid mixing occurs. This results in the release of the viral nucleocapsid and tegument proteins into the host cell’s cytoplasm. The gB receptor is primarily responsible for this (Figure 8) |
| With endocytosis, the enveloped particles through phagocytosis fuse with a vesicular membrane. Using similar interactions between gB, gD, gH, and gL, and host cell receptors, except all in an endosome, facilitate the fusion with host cell membrane. | With endocytosis, the enveloped particles through phagocytosis fuse with a vesicular membrane. Using similar interactions between gB, gD, gH, and gL, and host cell receptors, except all in an endosome, facilitate the fusion with host cell membrane. | ||
| Whether or not the virus using endocytosis or fusion at the plasma membrane is dependent upon individual cell types that they encounter. In Vero and Hep2 infected cells, there is no preference. However, in CHO, HeLa, RPE, human epidermal keratinocytes and KCjE cells, there is a preference for endocytosis. (Akhtar & Shukla, 2009) | Whether or not the virus using endocytosis or fusion at the plasma membrane is dependent upon individual cell types that they encounter. In Vero and Hep2 infected cells, there is no preference. However, in CHO, HeLa, RPE, human epidermal keratinocytes and KCjE cells, there is a preference for endocytosis. (Akhtar & Shukla, 2009) | ||
| - | <box 55% round| >{{ :complex.png?500|}} </box| Figure 9: The molecular interactions that facilitate HSV entry (Akhtar & Shukla, 2009)> | + | <box 45% round| >{{ :complex.png?500|}} </box| Figure 9: The molecular interactions that facilitate HSV entry (Akhtar & Shukla, 2009)> |
| ====== Post Entry Into Host Cell for HSV-1 & HSV-2 ====== | ====== Post Entry Into Host Cell for HSV-1 & HSV-2 ====== | ||
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| ====== Neural Cells Affected by HSV-1 ====== | ====== Neural Cells Affected by HSV-1 ====== | ||
| - | After the virus invades the epithelium and replicates, it travels to the trigeminal ganglia and surrounding sensory neurons in retrograde via nerve termini where the virus will be latent (Nicoll, Proenca, & Efstathiou, 2012). HSV1 can then reactivate due to physical and emotional stress, tissue damage, fever and ultraviolet light (Whitley & Roizman, 2001). During the latent phase, gene expression is suppressed, but increased during the reactivation phase through the expression of lytic cycle genes (Margolis, Imai, Yang, Vallas, & Krause, 2007). As a result, the virus then travels anterograde back to the epithelium producing lesions and sores (Liu, Khanna, Carriere, & Hendricks, 2001). | + | After the virus invades the epithelium and replicates, it travels to the trigeminal ganglia and surrounding sensory neurons in retrograde via nerve termini where the virus will be latent (Nicoll, Proenca, & Efstathiou, 2012). HSV-1 can then reactivate due to physical and emotional stress, tissue damage, fever and ultraviolet light (Whitley & Roizman, 2001). During the latent phase, gene expression is suppressed, but increased during the reactivation phase through the expression of lytic cycle genes (Margolis, Imai, Yang, Vallas, & Krause, 2007). As a result, the virus then travels anterograde back to the epithelium producing lesions and sores (Liu, Khanna, Carriere, & Hendricks, 2001). |
| ====== Neural Cells Affected by HSV-2 ====== | ====== Neural Cells Affected by HSV-2 ====== | ||
| - | <box 35% round right| >{{ :sacral.png?300|}} | + | <box 30% round right| >{{ :sacral.png?300|}} |
| </box| Figure 11: Distribution of the sacral nerve ganglia. (Vassantachart, & Menter, 2016)> | </box| Figure 11: Distribution of the sacral nerve ganglia. (Vassantachart, & Menter, 2016)> | ||
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| </box|Figure 10: The location and presentation of two lumbosacral clusters of vesicles in different stages of development and healing (Vassantachart, & Menter, 2016)> | </box|Figure 10: The location and presentation of two lumbosacral clusters of vesicles in different stages of development and healing (Vassantachart, & Menter, 2016)> | ||
| - | HSV1 and HSV2 are very similar except for differences in site-specific activation of symptoms. | + | HSV-1 and HSV-2 are very similar except for differences in site-specific activation of symptoms. |
| Once the virus has infected the cells, it enters a dormant state and can establish a lifelong latent infection in sensory neurons of the central nervous system that innervate the site of primary, and productive infection. The latency of the virus is important because it forms a reservoir of the virus to produce recurrent infections, disease, and transmission to other individuals. | Once the virus has infected the cells, it enters a dormant state and can establish a lifelong latent infection in sensory neurons of the central nervous system that innervate the site of primary, and productive infection. The latency of the virus is important because it forms a reservoir of the virus to produce recurrent infections, disease, and transmission to other individuals. | ||
| HSV-2 is associated with latent infection in the lumbosacral dorsal root ganglia (DRG), giving rise to the symptoms below the waist and predominantly in the genital area (Figure 10 and 11) (Kramer, Cook, Roth, Khu, Holman, Knipe, & Coen, 2003). | HSV-2 is associated with latent infection in the lumbosacral dorsal root ganglia (DRG), giving rise to the symptoms below the waist and predominantly in the genital area (Figure 10 and 11) (Kramer, Cook, Roth, Khu, Holman, Knipe, & Coen, 2003). | ||
| - | The specific effects that HSV-2 has on these neurons is still under extensive research. However, researchers do know that latent HSV-2 infection changes the gene expression in these neurons and attaches to neurons that are KH10 positive. HSV2 acts by inducing neuronal injury or by inducing a persistent immune response to the latent infection that induces the expression of cytokines which are also known to alter gene expression. Specifically, it can cause an increase of Stat1 in neurons. In addition, studies have shown that altered gene expression causes changes in Gprc1g, Gabbr1, Kcnab2, and Kcnc1 genes, affecting the neuronal excitability in an interconnected manner. The changing of the neuronal physiology alters sensations in this area and the latently infected ganglia exhibit alterations in ion channel functioning, leading to the commonly observed symptoms in the genitals (Kramer, Cook, Roth, Khu, Holman, Knipe, & Coen, 2003). | + | The specific effects that HSV-2 has on these neurons is still under extensive research. However, researchers do know that latent HSV-2 infection changes the gene expression in these neurons and attaches to neurons that are KH10 positive. HSV-2 acts by inducing neuronal injury or by inducing a persistent immune response to the latent infection that induces the expression of cytokines which are also known to alter gene expression. Specifically, it can cause an increase of Stat1 in neurons. In addition, studies have shown that altered gene expression causes changes in Gprc1g, Gabbr1, Kcnab2, and Kcnc1 genes, affecting the neuronal excitability in an interconnected manner. The changing of the neuronal physiology alters sensations in this area and the latently infected ganglia exhibit alterations in ion channel functioning, leading to the commonly observed symptoms in the genitals (Kramer, Cook, Roth, Khu, Holman, Knipe, & Coen, 2003). |
| ====== Crossover between HSV-1 and HSV-2 ====== | ====== Crossover between HSV-1 and HSV-2 ====== | ||
| The difference between the two virus types is in their latency stage. HSV-1 remains dormant in the nerve cells in the neck region, hence the outbursts on the face and mouth. HSV-2 remains dormant in the nerve cells located at the base of the spine, hence the outbursts in the genitals (Pierce, n.d.). Although they differ in where they remain dormant, it is possible and quite common for the viruses to crossover to different regions from the upper body to the lower body, and vice versa. Therefore, HSV-1 can cause genital herpes and HSV-2 can cause oral herpes. HSV-1 can cause genital herpes due to the fact that the lesions of the mouth also undergo the process of “shedding” and during oral sex, come into contact with mucosal membranes, gaining access to entering the body. This can also happen in a reverse fashion. If an individual has HSV-2 and oral sex is performed, the unaffected partner can contract oral herpes by being exposed to HSV-2 due to the same shedding process of the lesions. Therefore, allowing the virus to gain access to mucosal membranes in the mouth area (STDcheck, 2015). | The difference between the two virus types is in their latency stage. HSV-1 remains dormant in the nerve cells in the neck region, hence the outbursts on the face and mouth. HSV-2 remains dormant in the nerve cells located at the base of the spine, hence the outbursts in the genitals (Pierce, n.d.). Although they differ in where they remain dormant, it is possible and quite common for the viruses to crossover to different regions from the upper body to the lower body, and vice versa. Therefore, HSV-1 can cause genital herpes and HSV-2 can cause oral herpes. HSV-1 can cause genital herpes due to the fact that the lesions of the mouth also undergo the process of “shedding” and during oral sex, come into contact with mucosal membranes, gaining access to entering the body. This can also happen in a reverse fashion. If an individual has HSV-2 and oral sex is performed, the unaffected partner can contract oral herpes by being exposed to HSV-2 due to the same shedding process of the lesions. Therefore, allowing the virus to gain access to mucosal membranes in the mouth area (STDcheck, 2015). | ||
| - | In addition, it is important to note that HSV-1 and HSV-2 do invade different neurons - HSV1 being trigeminal ganglia and HSV2 being the lumbosacral dorsal root ganglia. However, HSV-1 is characterized by two different patterns of gene expression. When there is an abundant expression of lytic cycle genes, the HSV-1 virus is infective in some neurons, whereas in other neurons, latency is established. This is all controlled by which neurons express either MAb KH10 (productive infection), or MAb A5 (latent infection). Both of these factors are expressed predominantly on trigeminal ganglia, but also can be found on lumbosacral DSG. In contrast, HSV2 infects KH10-positive neurons which are primarily found in the lumbosacral DSG, but also in the trigeminal ganglia. Nonetheless, these viruses can take advantage of two different biological niches. Therefore, this phenomenon explains why it is possible to have crossovers between the two viruses, as well as why they are able to infect opposite areas of the body (Margolis, Lmai, Yang, Vallas, Krause, 2007). | + | In addition, it is important to note that HSV-1 and HSV-2 do invade different neurons - HSV-1 being trigeminal ganglia and HSV-2 being the lumbosacral dorsal root ganglia. However, HSV-1 is characterized by two different patterns of gene expression. When there is an abundant expression of lytic cycle genes, the HSV-1 virus is infective in some neurons, whereas in other neurons, latency is established. This is all controlled by which neurons express either MAb KH10 (productive infection), or MAb A5 (latent infection). Both of these factors are expressed predominantly on trigeminal ganglia, but also can be found on lumbosacral DSG. In contrast, HSV-2 infects KH10-positive neurons which are primarily found in the lumbosacral DSG, but also in the trigeminal ganglia. Nonetheless, these viruses can take advantage of two different biological niches. Therefore, this phenomenon explains why it is possible to have crossovers between the two viruses, as well as why they are able to infect opposite areas of the body (Margolis, Lmai, Yang, Vallas, Krause, 2007). |
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| <box 20% round left| >{{ :acyclovir.jpg?200|}}</box|Figure 12: Acyclovir Medication for treatment of Herpes Simplex Virus. Brand names include Avirax, and Zovirax (Jane, 2011).> | <box 20% round left| >{{ :acyclovir.jpg?200|}}</box|Figure 12: Acyclovir Medication for treatment of Herpes Simplex Virus. Brand names include Avirax, and Zovirax (Jane, 2011).> | ||
| - | <box 35% round left| >{{ :valacyclovir-hcl.jpg?400|}}</box|Figure 13: Valacyclovir HCl Medication, used for the treatment of Cold Sores (Oral Herpes) and Genital Herpes, as well as Shingles (HSVType 1, 2013).> | + | <box 35% round left| >{{ :valacyclovir-hcl.jpg?380|}}</box|Figure 13: Valacyclovir HCl Medication, used for the treatment of Cold Sores (Oral Herpes) and Genital Herpes, as well as Shingles (HSVType 1, 2013).> |
| <box 30% round left| >{{ :famciclovir.jpg?300|}}</box|Figure 14: Famciclovir Medication is also another treatment option for Genital Herpes, and Shingles (Doktor, 2018).> | <box 30% round left| >{{ :famciclovir.jpg?300|}}</box|Figure 14: Famciclovir Medication is also another treatment option for Genital Herpes, and Shingles (Doktor, 2018).> | ||
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| <box 65% round| >{{ :hamilton_services_page_3.png?700 |}}</box|Figure 18: This is a list of some of the Health Units that are available in Hamilton, Ontario (Hamilton, 2018).> | <box 65% round| >{{ :hamilton_services_page_3.png?700 |}}</box|Figure 18: This is a list of some of the Health Units that are available in Hamilton, Ontario (Hamilton, 2018).> | ||
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| + | ========= Conclusion ========= | ||
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| + | HSV-1 and HSV-2 most commonly infect humans. HSV-1 predominantly affects regions above the waist as the virus binds to A5 and KH10 receptors on the trigeminal ganglia located in the brain. HSV-2 predominantly affects regions below the waist as the virus binds to the KH10 receptors that are in abundance in the lumbosacral root ganglia located the base of the spine. Crossover between the two types occurs as well due to both ganglia having the KH10 receptor. Although HSV is not curable, there are numerous treatment options, with episodic and suppressive therapies being two in particular. | ||
| ========= References ========= | ========= References ========= | ||
