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Virus latency

Virus latency (or viral latency) is the ability of a pathogenic virus to lie dormant (latent) within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not eradicated. The virus can reactivate and begin producing large amounts of viral progeny (the lytic part of the viral life cycle) without the host becoming reinfected by new outside virus, and stays within the host indefinitely.

Virus latency is not to be confused with clinical latency during the incubation period when a virus is not dormant.

Contents

Episomal latency

Episomal latency refers to the use of genetic episomes during latency. In this latency type, viral genes are stabilized, floating in the cytoplasm or nucleus as distinct objects, either as linear or lariat structures. Episomal latency is more vulnerable to ribozymes or host foreign gene degradation than proviral latency (see below).

One example is herpes virus family, Herpesviridae, all of which establish latent infection. Herpes virus include chicken-pox virus and herpes simplex viruses (HSV-1, HSV-2), all of which establish episomal latency in neurons and leave linear genetic material floating in the cytoplasm. The Gammaherpesvirinae subfamily is associated with episomal latency established in cells of the immune system, such as B-cells in the case of Epstein–Barr virus. Epstein–Barr virus lytic reactivation (which can be due to chemotherapy or radiation) can result in genome instability and cancer. In the case of herpes simplex (HSV), the virus has been shown to fuse with DNA in neurons, such as nerve ganglia or neurons, and HSV reactivates upon even minor chromatin loosening with stress, although the chromatin compacts (becomes latent) upon oxygen and nutrient deprivation.

Cytomegalovirus (CMV) establishes latency in myeloid progenitor cells, and is reactivated by inflammation. Immunosuppression and critical illness (sepsis in particular) often results in CMV reactivation. CMV reactivation is commonly seen in patients with severe colitis.

Advantages of episomal latency include the fact that the virus may not need to enter the nucleus, and hence may avoid nuclear domain 10 (ND10) from activating interferon via that pathway.

Disadvantages include more exposure to cellular defenses, leading to possible degradation of viral gene via cellular enzymes.

Reactivation may be due to stress, UV, etc.

Proviral latency

A provirus is a virus genome that is integrated into the DNA of a host cell.

Advantages include automatic host cell division results in replication of the virus's genes, and the fact that it is nearly impossible to remove an integrated provirus from an infected cell without killing the cell.

A disadvantage of this method is the need to enter the nucleus (and the need for packaging proteins that will allow for that). However, viruses that integrate into the host cell's genome can stay there as long as the cell lives.

One of the best-studied viruses that does this is HIV. HIV uses reverse transcriptase to create a DNA copy of its RNA genome. HIV latency allows the virus to largely avoid the immune system. Like other viruses that go latent, it does not typically cause symptoms while latent. Unfortunately, HIV in proviral latency is nearly impossible to target with antiretroviral drugs.

Maintaining latency

Both proviral and episomal latency may require maintenance for continued infection and fidelity of viral genes. Latency is generally maintained by viral genes expressed primarily during latency. Expression of these latency-associated genes may function to keep the viral genome from being digested by cellular ribozymes or being found out by the immune system. Certain viral gene products (RNA transcripts such as non-coding RNAs and proteins) may also inhibit apoptosis or induce cell growth and division to allow more copies of the infected cell to be produced.

An example of such a gene product is the latency associated transcripts (LAT) in herpes simplex virus, which interfere with apoptosis by downregulating a number of host factors, including major histocompatibility complex (MHC) and inhibiting the apoptotic pathway.

A certain type of latency could be ascribed to the endogenous retroviruses. These viruses have incorporated into the human genome in the distant past, and are now transmitted through reproduction. Generally these types of viruses have become highly evolved, and have lost the expression of many gene products. Some of the proteins expressed by these viruses have co-evolved with host cells to play important roles in normal processes.

While viral latency exhibits no active viral shedding nor causes any pathologies or symptoms, the virus is still able to reactivate via external activators (sunlight, stress, etc) to cause an acute infection. In the case of herpes simplex virus, which generally infects an individual for life, a serotype of the virus reactivates occasionally to cause cold sores. Although the sores are quickly resolved by the immune system, they may be a minor annoyance from time to time. In the case of varicella zoster virus, after an initial acute infection (chickenpox) the virus lies dormant until reactivated as herpes zoster.

More serious ramifications of a latent infection could be the possibility of transforming the cell, and forcing the cell into uncontrolled cell division. This is a result of the random insertion of the viral genome into the host's own gene and expression of host cellular growth factors for the benefit of the virus. In a notable event, this actually happened during gene therapy through the use of retroviral vectors at the Necker Hospital in Paris, where twenty young boys received treatment for a genetic disorder, after which five developed leukemia-like syndromes.

This is also seen with infections of the human papilloma virus in which persistent infection may lead to cervical cancer as a result of cellular transformation.

In the field of HIV research, proviral latency in specific long-lived cell types is the basis for the concept of one or more viral reservoirs, referring to locations (cell types or tissues) characterized by persistence of latent virus. Specifically, the presence of replication-competent HIV in resting CD4-positive T cells allows this virus to persist for years without evolving despite prolonged exposure to antiretroviral drugs. This latent reservoir of HIV may explain the inability of antiretroviral treatment to cure HIV infection.

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Virus latency
Virus latency Language Watch Edit Virus latency or viral latency is the ability of a pathogenic virus to lie dormant latent within a cell denoted as the lysogenic part of the viral life cycle 1 A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection Latency is the phase in certain viruses life cycles in which after initial infection proliferation of virus particles ceases However the viral genome is not eradicated The virus can reactivate and begin producing large amounts of viral progeny the lytic part of the viral life cycle without the host becoming reinfected by new outside virus and stays within the host indefinitely 2 Virus latency is not to be confused with clinical latency during the incubation period when a virus is not dormant Contents 1 Mechanisms 1 1 Episomal latency 1 2 Proviral latency 1 3 Maintaining latency 2 Ramifications 3 See also 4 ReferencesMechanisms EditEpisomal latency Edit Episomal latency refers to the use of genetic episomes during latency In this latency type viral genes are stabilized floating in the cytoplasm or nucleus as distinct objects either as linear or lariat structures Episomal latency is more vulnerable to ribozymes or host foreign gene degradation than proviral latency see below One example is herpes virus family Herpesviridae all of which establish latent infection Herpes virus include chicken pox virus and herpes simplex viruses HSV 1 HSV 2 all of which establish episomal latency in neurons and leave linear genetic material floating in the cytoplasm 3 The Gammaherpesvirinae subfamily is associated with episomal latency established in cells of the immune system such as B cells in the case of Epstein Barr virus 3 4 Epstein Barr virus lytic reactivation which can be due to chemotherapy or radiation can result in genome instability and cancer 5 In the case of herpes simplex HSV the virus has been shown to fuse with DNA in neurons such as nerve ganglia 6 or neurons and HSV reactivates upon even minor chromatin loosening with stress 7 although the chromatin compacts becomes latent upon oxygen and nutrient deprivation 8 Cytomegalovirus CMV establishes latency in myeloid progenitor cells and is reactivated by inflammation 9 Immunosuppression and critical illness sepsis in particular often results in CMV reactivation 10 CMV reactivation is commonly seen in patients with severe colitis 11 Advantages of episomal latency include the fact that the virus may not need to enter the nucleus and hence may avoid nuclear domain 10 ND10 from activating interferon via that pathway Disadvantages include more exposure to cellular defenses leading to possible degradation of viral gene via cellular enzymes 12 Reactivation may be due to stress UV etc 13 Proviral latency Edit A provirus is a virus genome that is integrated into the DNA of a host cell Advantages include automatic host cell division results in replication of the virus s genes and the fact that it is nearly impossible to remove an integrated provirus from an infected cell without killing the cell 14 A disadvantage of this method is the need to enter the nucleus and the need for packaging proteins that will allow for that However viruses that integrate into the host cell s genome can stay there as long as the cell lives One of the best studied viruses that does this is HIV HIV uses reverse transcriptase to create a DNA copy of its RNA genome HIV latency allows the virus to largely avoid the immune system Like other viruses that go latent it does not typically cause symptoms while latent Unfortunately HIV in proviral latency is nearly impossible to target with antiretroviral drugs Maintaining latency Edit Both proviral and episomal latency may require maintenance for continued infection and fidelity of viral genes Latency is generally maintained by viral genes expressed primarily during latency Expression of these latency associated genes may function to keep the viral genome from being digested by cellular ribozymes or being found out by the immune system Certain viral gene products RNA transcripts such as non coding RNAs and proteins may also inhibit apoptosis or induce cell growth and division to allow more copies of the infected cell to be produced 15 An example of such a gene product is the latency associated transcripts LAT in herpes simplex virus which interfere with apoptosis by downregulating a number of host factors including major histocompatibility complex MHC and inhibiting the apoptotic pathway 16 A certain type of latency could be ascribed to the endogenous retroviruses These viruses have incorporated into the human genome in the distant past and are now transmitted through reproduction Generally these types of viruses have become highly evolved and have lost the expression of many gene products 17 Some of the proteins expressed by these viruses have co evolved with host cells to play important roles in normal processes 18 Ramifications EditWhile viral latency exhibits no active viral shedding nor causes any pathologies or symptoms the virus is still able to reactivate via external activators sunlight stress etc to cause an acute infection In the case of herpes simplex virus which generally infects an individual for life a serotype of the virus reactivates occasionally to cause cold sores Although the sores are quickly resolved by the immune system they may be a minor annoyance from time to time In the case of varicella zoster virus after an initial acute infection chickenpox the virus lies dormant until reactivated as herpes zoster More serious ramifications of a latent infection could be the possibility of transforming the cell and forcing the cell into uncontrolled cell division This is a result of the random insertion of the viral genome into the host s own gene and expression of host cellular growth factors for the benefit of the virus In a notable event this actually happened during gene therapy through the use of retroviral vectors at the Necker Hospital in Paris where twenty young boys received treatment for a genetic disorder after which five developed leukemia like syndromes 19 This is also seen with infections of the human papilloma virus in which persistent infection may lead to cervical cancer as a result of cellular transformation 20 21 22 In the field of HIV research proviral latency in specific long lived cell types is the basis for the concept of one or more viral reservoirs referring to locations cell types or tissues characterized by persistence of latent virus Specifically the presence of replication competent HIV in resting CD4 positive T cells allows this virus to persist for years without evolving despite prolonged exposure to antiretroviral drugs 23 This latent reservoir of HIV may explain the inability of antiretroviral treatment to cure HIV infection 23 24 25 26 See also Edit Viruses portal Slow virusReferences Edit Villarreal Luis P 2005 Viruses and the Evolution of Life Washington ASM Press N J Dimmock et al Introduction to Modern Virology 6th edition Blackwell Publishing 2007 a b Minarovits J 2006 Epigenotypes of Latent Herpesvirus Genomes DNA Methylation Development Genetic Disease and Cancer Current Topics in Microbiology and Immunology 310 pp 61 80 doi 10 1007 3 540 31181 5 5 ISBN 978 3 540 31180 5 PMID 16909907 Souza TA Stollar BD Sullivan JL Luzuriaga K Thorley Lawson DA 2007 09 01 Influence of EBV on the peripheral blood memory B cell compartment Journal of Immunology 179 5 3153 60 doi 10 4049 jimmunol 179 5 3153 PMID 17709530 Li H Liu S Hu J Luo X Li N M Bode A Cao Y 2016 Epstein Barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis International Journal of Biological Sciences 12 11 1309 1318 doi 10 7150 ijbs 16564 PMC 5118777 PMID 27877083 Thellman NM Triezenberg SJ 2017 Herpes Simplex Virus Establishment Maintenance and Reactivation In Vitro Modeling of Latency Pathogens 6 3 E28 doi 10 3390 pathogens6030028 PMC 5617985 PMID 28644417 Discovery shows how herpes simplex virus reactivates in neurons to trigger disease 2015 12 21 Starve a Cell Compact Its DNA GEN GEN 2015 11 10 Dupont L Reeves MB 2016 Cytomegalovirus latency and reactivation recent insights into an age old problem Reviews in Medical Virology 26 2 75 89 doi 10 1002 rmv 1862 PMC 5458136 PMID 26572645 Cook CH 2007 Cytomegalovirus reactivation in immunocompetent patients a call for scientific prophylaxis The Journal of Infectious Diseases 196 9 1273 1275 doi 10 1086 522433 PMID 17922387 Sager K Alam S Bond A Chinnappan L Probert CS 2015 Review article cytomegalovirus and inflammatory bowel disease Alimentary Pharmacology amp Therapeutics 41 8 725 733 doi 10 1111 apt 13124 PMID 25684400 Burton EA Fink DJ Glorioso JC Dec 2002 Gene delivery using herpes simplex virus vectors DNA Cell Biol 21 12 915 36 doi 10 1089 104454902762053864 PMID 12573050 Preston Chris M Efstathiou Stacey 21 September 2018 Molecular basis of HSV latency and reactivation In Arvin Ann Campadelli Fiume Gabriella Mocarski Edward Moore Patrick S Roizman Bernard Whitley Richard Yamanishi Koichi eds Human Herpesviruses Biology Therapy and Immunoprophylaxis Cambridge University Press ISBN 9780521827140 PMID 21348106 via PubMed Marcello A Latency the hidden HIV 1 challenge Retrovirology 2006 Jan 16 3 1 7 Divito S Cherpes TL Hendricks RL 2006 A triple entente virus neurons and CD8 T cells maintain HSV 1 latency Immunol Res 36 1 3 119 26 doi 10 1385 ir 36 1 119 PMID 17337772 S2CID 6150236 Carpenter D Hsiang C Brown DJ Jin L Osorio N Benmohamed L Jones C Wechsler SL Dec 2007 Stable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis Virology 369 1 12 8 doi 10 1016 j virol 2007 07 023 PMC 2276668 PMID 17727910 Buzdin A Nov 2007 Human specific endogenous retroviruses ScientificWorldJournal 7 1848 68 doi 10 1100 tsw 2007 270 PMC 5901341 PMID 18060323 Hayashida K Omagari K Masuda JI Kohno S 2007 An integrase of endogenous retrovirus is involved in maternal mitochondrial DNA inheritance of the human mammal Biochem Biophys Res Commun 366 1 206 211 doi 10 1016 j bbrc 2007 11 127 hdl 10069 22710 PMID 18054325 Hacein Bey Abina S Garrigue A Wang GP Soulier J Lim A Morillon E Clappier E Caccavelli L Delabesse E Beldjord K Asnafi V MacIntyre E Dal Cortivo L Radford I Brousse N Sigaux F Moshous D Hauer J Borkhardt A Belohradsky BH Wintergerst U Velez MC Leiva L Sorensen R Wulffraat N Blanche S Bushman FD Fischer A Cavazzana Calvo M September 2008 Insertional oncogenesis in 4 patients after retrovirus mediated gene therapy of SCID X1 The Journal of Clinical Investigation 118 9 3132 42 doi 10 1172 JCI35700 PMC 2496963 PMID 18688285 Wang XG Revskaya E Bryan RA Strickler HD Burk RD Casadevall A Dadachova E Oct 2007 Treating cancer as an infectious disease viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology PLOS ONE 2 10 e1114 Bibcode 2007PLoSO 2 1114W doi 10 1371 journal pone 0001114 PMC 2040508 PMID 17971877 Molho Pessach V Lotem M 2007 Viral carcinogenesis in skin cancer Environmental Factors in Skin Diseases Curr Probl Dermatol Current Problems in Dermatology 35 pp 39 51 doi 10 1159 000106409 ISBN 978 3 8055 8313 8 PMID 17641489 S2CID 14519920 Carrillo Infante C Abbadessa G Bagella L Giordano A Jun 2007 Viral infections as a cause of cancer review Int J Oncol 30 6 1521 8 doi 10 3892 ijo 30 6 1521 PMID 17487374 a b Blankson JN Persaud D Siliciano RF 2002 The challenge of viral reservoirs in HIV 1 infection Annu Rev Med 53 557 93 doi 10 1146 annurev med 53 082901 104024 PMID 11818490 Finzi D Hermankova M Pierson T et al November 1997 Identification of a reservoir for HIV 1 in patients on highly active antiretroviral therapy Science 278 5341 1295 300 Bibcode 1997Sci 278 1295F doi 10 1126 science 278 5341 1295 PMID 9360927 Persaud D Pierson T Ruff C et al April 2000 A stable latent reservoir for HIV 1 in resting CD4 T lymphocytes in infected children J Clin Invest 105 7 995 1003 doi 10 1172 JCI9006 PMC 377486 PMID 10749578 Chun TW Fauci AS September 1999 Latent reservoirs of HIV obstacles to the eradication of virus Proc Natl Acad Sci U S A 96 20 10958 61 Bibcode 1999PNAS 9610958C doi 10 1073 pnas 96 20 10958 PMC 34225 PMID 10500107 Retrieved from https en wikipedia org w index php title Virus latency amp oldid 1046005437, wikipedia, wiki, book,

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