Gammaherpesvirinae

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Gammaherpesvirinae
Epstein Barr Virus virions EM 10.1371 journal.pbio.0030430.g001-L.JPG
Electron micrograph of two Human gammaherpesvirus 4 virions (viral particles) showing round capsids loosely surrounded by the membrane envelope
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Duplodnaviria
Kingdom: Heunggongvirae
Phylum: Peploviricota
Class: Herviviricetes
Order: Herpesvirales
Family: Orthoherpesviridae
Subfamily:Gammaherpesvirinae
Genera

See text

Gammaherpesvirinae is a subfamily of viruses in the order Herpesvirales and in the family Herpesviridae . Viruses in Gammaherpesvirinae are distinguished by reproducing at a more variable rate than other subfamilies of Herpesviridae. Mammals serve as natural hosts. There are 43 species in this subfamily, divided among 7 genera with three species unassigned to a genus. Diseases associated with this subfamily include: HHV-4: infectious mononucleosis. HHV-8: Kaposi's sarcoma. [1] [2]

Contents

Taxonomy

Herpesviruses represent a group of double-stranded DNA viruses distributed widely within the animal kingdom. The family Herpesviridae, which contains eight viruses that infect humans, is the most extensively studied group within this order and comprises three subfamilies, namely Alphaherpesvirinae , Betaherpesvirinae and Gammaherpesvirinae.

Within the Gammaherpesvirinae there are a number of unclassified viruses including Cynomys herpesvirus 1 (CynGHV-1) [3] Elephantid herpesvirus 3, Elephantid herpesvirus 4, Elephantid herpesvirus 5, Procavid herpesvirus 1, Trichechid herpesvirus 1 [4] and Common bottlenose dolphin gammaherpesvirus 1. [5]

Genera

Gammaherpesvirinae consists of the following seven genera: [2]

Additionally, the following three species are unassigned to a genus: [2]

Structure

Viruses in Gammaherpesvirinae are enveloped, with icosahedral, spherical to pleomorphic, and round geometries, and T=16 symmetry. The diameter is around 150-200 nm. Genomes are linear and non-segmented, around 180kb in length. [1]

GenusStructureSymmetryCapsidGenomic arrangementGenomic segmentation
MacavirusSpherical pleomorphicT=16EnvelopedLinearMonopartite
PercavirusSpherical pleomorphicT=16EnvelopedLinearMonopartite
LymphocryptovirusSpherical pleomorphicT=16EnvelopedLinearMonopartite
RhadinovirusSpherical pleomorphicT=16EnvelopedLinearMonopartite

Life cycle

The main stages in the lifecycle of Gamma herpes virus are namely
• Virus attachment and entry
• Viral DNA injection through nuclear pore complex (NPC) into nucleus
• Assembly of nucleocapsids and encapsidation of viral genome
• Primary envelopment, invaginations of nuclear membranes and nuclear egress
• Tegumentation and secondary envelopment in the cytoplasm
• Egress and extracellular virions release [6] [7]

GenusHost detailsTissue tropismEntry detailsRelease detailsReplication siteAssembly siteTransmission
MacavirusMammalsT-lymphocytesGlycoproteinsBuddingNucleusNucleusNasal and ocular secretion
PercavirusMammalsB-lymphocytesGlycoproteinsBuddingNucleusNucleusSex; saliva
LymphocryptovirusHumans; mammalsB-lymphocytesGlycoproteinsBuddingNucleusNucleusSaliva
RhadinovirusHumans; mammalsB-lymphocytesGlycoproteinsBuddingNucleusNucleusSex; saliva

Lytic cycle

The lytic cycle of the gammaherpesviruses is initiated only on rare occasions. [7] [8] Therefore, the least contribution to pathogenicity has to be expected from this stage. The ORFs expressed during that stage are further divided into immediate-early, early, and late. Promoter activation mediated by these proteins has also a strong effect on DNA synthesis from the origins of lytic DNA replication. As a result, virions are generated and released from the productively infected cells. [9]

Immune evasion strategies

Viruses that establish lifelong latent infections must ensure that the viral genome is maintained within the latently infected cell throughout the life of the host, yet at the same time must also be capable of avoiding elimination by the immune surveillance system especially must avoid being detected by host CD8+ cytotoxic T lymphocytes (CTLs). The gamma-herpesviruses are characteristically latent in lymphocytes and drive the proliferation that requires the expression of latent viral antigens. [10] The majority of gammaherpesviruses encode a specific protein that is critical for maintenance of the viral genome within latently infected cells termed the genome maintenance protein (GMP). During latency, the genome persists in the nucleus of the infected cells as a circular episomal element. GMPs are DNA-binding proteins that ensure that, as the host cell progresses through mitosis, the viral episomes are partitioned to daughter cells. This provides continuous existence of the viral genome within the host cells. [11] [12]

MHV68 in genetically modified mice is used as a model for studying infection and host responses. Stable lifelong latency is a hallmark of the chronic phase of MHV68 infection. The spleen is a major infection site. The episomal maintenance protein for MHV68 is a latency-associated nuclear antigen (mLANA; ORF73). M2 protein mediates signaling pathways of infected B cells by interacting with SH2- and SH3-containing proteins. Host factors have been identified that can promote or antagonize MHV68 latency and reactivation. [7]

Human health

Gammaherpesviruses are of primary interest due to the two human viruses, EBV (Epstein–Barr virus) and KSHV (Kaposi's sarcoma-associated herpesvirus) and the diseases they cause. The gammaherpesviruses replicate and persist in lymphoid cells but some are capable of undergoing lytic replication in epithelial or fibroblast cells. Gammaherpesviruses may be a cause of chronic fibrotic lung diseases in humans and in animals. [13]

Murid herpesvirus 68 is an important model system for the study of gammaherpesviruses with tractable genetics. [7] The gammaherpesviruses, including HVS, EBV, KSHV, and RRV, are capable of establishing latent infection in lymphocytes. [11]

Attenuated virus mutants represent a promising approach towards gamma-herpesvirus infection control. Surprisingly, latency-deficient and, therefore, apathogenic MHV-68 mutants are found to be highly effective vaccines against these viruses. [10] Research in this area is almost exclusively performed using MHV68 as KSHV and EBV (the major human pathogens of this family) do not productively infect model organisms typically used for this type of experimentation.

Growth de-regulating genes

Herpesviruses have large genomes containing a wide array of genes. Although the first ORF in these gammaherpesviruses have oncogenic potential, other viral genes may also play a role in viral transformation. A striking feature of the four gammaherpesviruses is that they contain distinct ORFs involved in lymphocyte signaling events. At the left end of each viral genome are located ORFs encoding distinct transforming proteins. Gammaherpesvirus genes are capable of modulating cellular signals such that cell proliferation and viral replication occur at the appropriate times in the viral life cycle. [11]

Related Research Articles

<i>Cytomegalovirus</i> Genus of viruses

Cytomegalovirus (CMV) is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans and other primates serve as natural hosts. The 11 species in this genus include human betaherpesvirus 5, which is the species that infects humans. Diseases associated with HHV-5 include mononucleosis and pneumonia, and congenital CMV in infants can lead to deafness and ambulatory problems.

<span class="mw-page-title-main">Epstein–Barr virus</span> Virus of the herpes family

The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. Epstein-Barr virus (EBV) is the first identified oncogenic virus, which establishes permanent infection in humans. EBV causes infectious mononucleosis and is also tightly linked to many malignant diseases. Various vaccine formulations underwent testing in different animals or in humans. However, none of them was able to prevent EBV infection and no vaccine has been approved to date.

Rhadinovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Gammaherpesvirinae. Humans and other mammals serve as natural hosts. There are 12 species in this genus. Diseases associated with this genus include: Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, caused by Human gammaherpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). The term rhadino comes from the Latin fragile, referring to the tendency of the viral genome to break apart when it is isolated.

<span class="mw-page-title-main">Kaposi's sarcoma-associated herpesvirus</span> Species of virus

Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is Human gammaherpesvirus 8, or HHV-8 in short. Like other herpesviruses, its informal names are used interchangeably with its formal ICTV name. This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients, as well as primary effusion lymphoma, HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. It is one of seven currently known human cancer viruses, or oncoviruses. Even after many years since the discovery of KSHV/HHV8, there is no known cure for KSHV associated tumorigenesis.

Virus latency is the ability of a pathogenic virus to lie dormant 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 without the host becoming reinfected by new outside virus, and stays within the host indefinitely.

<span class="mw-page-title-main">Human herpesvirus 6</span> Informal grouping of viruses which caused human herpesvirus 6 Infection

Human herpesvirus 6 (HHV-6) is the common collective name for human betaherpesvirus 6A (HHV-6A) and human betaherpesvirus 6B (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host.

HHV Latency Associated Transcript is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus (HHV) infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA. LAT regulates the viral genome and interferes with the normal activities of the infected host cell.

<i>Herpesviridae</i> Family of DNA viruses

Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ἕρπειν, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections.

<span class="mw-page-title-main">Herpes simplex virus</span> Species of virus

Herpes simplex virus1 and 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.

<span class="mw-page-title-main">Duck plague</span> Disease caused by Anatid alphaherpesvirus 1

Duck plague is a worldwide disease caused by Anatid alphaherpesvirus 1 (AnHV-1) of the family Herpesviridae that causes acute disease with high mortality rates in flocks of ducks, geese, and swans. It is spread both vertically and horizontally—through contaminated water and direct contact. Migratory waterfowl are a major factor in the spread of this disease as they are often asymptomatic carriers of disease. The incubation period is three to seven days. Birds as young as one week old can be infected. DEV is not zoonotic.

Betaherpesvirinae is a subfamily of viruses in the order Herpesvirales and in the family Herpesviridae. Mammals serve as natural hosts. There are 26 species in this subfamily, divided among 5 genera. Diseases associated with this subfamily include: human cytomegalovirus (HHV-5): congenital CMV infection; HHV-6: 'sixth disease' ; HHV-7: symptoms analogous to the 'sixth disease'.

<i>Lymphocryptovirus</i> Genus of viruses

Lymphocryptovirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Gammaherpesvirinae. This genus includes the human-infecting Human gammaherpesvirus 4, as well as viruses that infect both Old World monkeys and New World monkeys. Other names for the Lymphocryptovirus genus include Lymphocryptoviridae and gamma-1 herpesviruses. There are nine species in this genus. Diseases associated with this genus include: mononucleosis, Burkitt's lymphoma, and nasopharyngeal carcinoma.

Murid gammaherpesvirus 4 (MuHV-4) is a species of virus in the genus Rhadinovirus. It is a member of the subfamily Gammaherpesvirinae in the family Herpesviridae. This species infects mice via the nasal passages and causes an acute infectious mononucleosis-like syndrome with elevated levels of leukocytes, and shifts in the relative proportion of lymphocytes along with the appearance of atypical mononuclear cells. Murid gammaherpesvirus 4 currently serves as a model for study of human gammaherpesvirus pathogenesis.

Murid gammaherpesvirus 68 (MuHV-68) is an isolate of the virus species Murid gammaherpesvirus 4, a member of the genus Rhadinovirus. It is a member of the subfamily Gammaherpesvirinae in the family of Herpesviridae. MuHV-68 serves as a model for study of human gammaherpesviruses which cause significant human disease including B-cell lymphoma and Kaposi's sarcoma. The WUMS strain of MuHV-68 was fully sequenced and annotated in 1997, and the necessity of most of its genes in viral replication was characterized by random transposon mutagenesis.

<i>Herpesvirales</i> Order of viruses

The Herpesvirales is an order of dsDNA viruses with animal hosts, characterised by a common morphology consisting of an icosahedral capsid enclosed in a glycoprotein-containing lipid envelope. Common infections in humans caused by members of this order include cold sores, genital herpes, chickenpox, shingles, and glandular fever. Herpesvirales is the sole order in the class Herviviricetes, which is the sole class in the phylum Peploviricota.

<span class="mw-page-title-main">Epigenetics of human herpesvirus latency</span>

Human herpes viruses, also known as HHVs, are part of a family of DNA viruses that cause several diseases in humans. One of the most notable functions of this virus family is their ability to enter a latent phase and lay dormant within animals for extended periods of time. The mechanism that controls this is very complex because expression of viral proteins during latency is decreased a great deal, meaning that the virus must have transcription of its genes repressed. There are many factors and mechanisms that control this process and epigenetics is one way this is accomplished. Epigenetics refers to persistent changes in expression patterns that are not caused by changes to the DNA sequence. This happens through mechanisms such as methylation and acetylation of histones, DNA methylation, and non-coding RNAs (ncRNA). Altering the acetylation of histones creates changes in expression by changing the binding affinity of histones to DNA, making it harder or easier for transcription machinery to access the DNA. Methyl and acetyl groups can also act as binding sites for transcription factors and enzymes that further modify histones or alter the DNA itself.

Macavirus is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Gammaherpesvirinae. Mammals serve as natural hosts. There are nine species in this genus. Diseases associated with this genus include: inapparent infection in their reservoir hosts, but fatal lymphoproliferative disease when they infect MCF-susceptible hosts, including cattle, deer, bison, water buffalo and pigs.

HSV epigenetics is the epigenetic modification of herpes simplex virus (HSV) genetic code.

Macacine gammaherpesvirus 4 (McHV-4), commonly known as rhesus lymphocryptovirus (RLV), is a species of virus in the genus Lymphocryptovirus, subfamily Gammaherpesvirinae, family Herpesviridae, and order Herpesvirales.

<i>Duplodnaviria</i> Realm of viruses

Duplodnaviria is a realm of viruses that includes all double-stranded DNA viruses that encode the HK97 fold major capsid protein. The HK97 fold major capsid protein is the primary component of the viral capsid, which stores the viral deoxyribonucleic acid (DNA). Viruses in the realm also share a number of other characteristics, such as an icosahedral capsid, an opening in the viral capsid called a portal, a protease enzyme that empties the inside of the capsid prior to DNA packaging, and a terminase enzyme that packages viral DNA into the capsid.

References

  1. 1 2 "Viral Zone". ExPASy. Retrieved 15 June 2015.
  2. 1 2 3 "Virus Taxonomy: 2020 Release". International Committee on Taxonomy of Viruses (ICTV). March 2021. Retrieved 10 May 2021.
  3. ↑ Nagamine B, Jones L, Tellgren-Roth C, Cavender J, Bratanich AC (2011) A novel gammaherpesvirus isolated from a black-tailed prairie dog (Cynomys ludovicianus). Arch Virol
  4. ↑ Wellehan JF, Johnson AJ, Childress AL, Harr KE, Isaza R (2008) Six novel gammaherpesviruses of Afrotheria provide insight into the early divergence of the Gammaherpesvirinae. Vet Microbiol 127(3-4):249-257
  5. ↑ Davison AJ, Subramaniam K, Kerr K, Jacob JM, Landrau-Giovannetti N, Walsh MT, Wells RS, Waltzek TB (2017) Genome sequence of a gammaherpesvirus from a common bottlenose dolphin (Tursiops truncatus). Genome Announc 5(31)
  6. ↑ Peng, L.; Ryazantsev, S.; Sun, R.; Zhou, Z. H. (2010). "Three-Dimensional Visualization of Gammaherpesvirus Life Cycle in Host Cells by Electron Tomography". Structure. 18 (1): 47–58. doi:10.1016/j.str.2009.10.017. PMC   2866045 . PMID   20152152.
  7. 1 2 3 4 Wang, Yiping; Tibbetts, Scott A.; Krug, Laurie T. (29 September 2021). "Conquering the Host: Determinants of Pathogenesis Learned from Murine Gammaherpesvirus 68". Annual Review of Virology. 8 (1): 349–371. doi: 10.1146/annurev-virology-011921-082615 . ISSN   2327-056X. PMC   9153731 . PMID   34586873.
  8. ↑ Oehmig, A.; Fraefel, C.; Breakefield, X. (2004). "Update on herpesvirus amplicon vectors". Mol Ther. 10 (4): 630–643. doi: 10.1016/j.ymthe.2004.06.641 . PMID   15451447 . Retrieved 10 November 2021.
  9. ↑ Ackermann, M. (2006). "Pathogenesis of gammaherpesvirus infections". Veterinary Microbiology. 113 (3–4): 211–222. doi:10.1016/j.vetmic.2005.11.008. PMID   16332416.
  10. 1 2 Stevenson, P. G. (2004). "Immune evasion by gamma-herpesviruses". Current Opinion in Immunology. 16 (4): 456–462. doi:10.1016/j.coi.2004.05.002. PMID   15245739.
  11. 1 2 3 Blake, N. (2010). "Immune evasion by gammaherpesvirus genome maintenance proteins". Journal of General Virology. 91 (4): 829–846. doi: 10.1099/vir.0.018242-0 . PMID   20089802.
  12. ↑ Sorel, Océane; Dewals, Benjamin G. (2019). "The Critical Role of Genome Maintenance Proteins in Immune Evasion During Gammaherpesvirus Latency". Frontiers in Microbiology. 9: 3315. doi: 10.3389/fmicb.2018.03315 . ISSN   1664-302X. PMC   6333680 . PMID   30687291.
  13. ↑ Williams, KJ (March 2014). "Gammaherpesviruses and Pulmonary Fibrosis: Evidence From Humans, Horses, and Rodents". Veterinary Pathology. 51 (2): 372–384. doi:10.1177/0300985814521838. PMID   24569614. S2CID   22704874.
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