Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Classification
3. Structure
3.1. Viral Particle
3.2. Viral Genome
4. Viral Replication
4.1. Entry in the Cell
4.2. KSHV Latent Cycle
4.3. KSHV Lytic Cycle
5. Epidemiology
5.1. KSHV Seroprevalence and Transmission
5.1.1. Transmission in Countries with Low Seroprevalence
5.1.2. Transmission in Endemic Regions
5.2. Molecular Epidemiology
5.2.1. ORF-K1
5.2.2. Other Genes
5.2.3. Molecular Diversity and Pathogenicity
6. KSHV Oncogenesis and Kaposi’s Sarcoma
6.1. KSHV, Cells Tropism and Risk Factors
6.2. KSHV Latency Proteins and Oncogenesis
6.3. Lytic Proteins and Oncogenesis
7. Rationale and Feasibility of KSHV Vaccine
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Low | Intermediate | High | |
---|---|---|---|
World region | North America Western Europe Eastern Asia | Mediterranean basin Eastern Europe Southern America Western Africa | Central Africa Eastern Africa |
KSHV Seroprevalence | <10% | 10–30% | >50% |
Transmission | Sexual Iatrogenic | Sexual Iatrogenic Nonsexual | Childhood Sexual |
Risk factors | Risky sexual behavior: STIs including HIV, number of different sexual partners Use of poppers? | Infectious agents (malaria)? Soils rich in metals? Chemical substances from plants? | Infectious agents (malaria)? Soils rich in metals? Chemical substances from plants? Transfusion |
At-risk population | MSM Organ transplant patients | MSM Organ transplant patients Elderly men | Children Elderly men Low socio-economic level |
Proteins or RNA | Gene | Viral Cycle | Cellular Homologs | Essential Functions |
---|---|---|---|---|
LANA-1 | ORF73 | Latent | - | Inhibition of lytic cycle by inhibiting the expression of RTA [177] Sequestration of KSHV episome in nucleus and transmission to daughters’ cell during mitosis Inhibition of apoptosis by interacting with p53 and pRB Recruitment of DNA methyltransferase [178] Recruitment of host PRC and KAP1 to suppress lytic gene expression [179,180] Cytoplasmic isoform of LANA-1 inhibits cGAS to promote KSHV reactivation [181] |
v-cyclin | ORF72 | Latent | Cyclin D2 | Cell proliferation: v-cyclin-CDK6 => inhibition of p21 and p27 Cell transformation |
v-FLIP | ORF71 | Latent | FLICE | Inhibition of apoptosis Activation of NF-kB pathway by interaction with NEMO [182] Inhibition of RBP-Jk (co-activator of RTA) |
miRNA miRNA-K7-5p miRNA-K9-5p miRNA K1 | - - - miR-K11 | Latent | - | Immunomodulation, immune escape, inhibition of apoptosis Post transcriptional inhibition of RTA expression Post transcriptional inhibition of RTA expression Activation of NF-kB pathway |
Kaposin | ORF-K12 | Latent | - | Cell transformation Activation of p18/MK2 pathways |
LANA-2 /v-IRF3 | ORF 10.5 | Latent | - | Inhibition of p53 pathway Immune escape |
RTA | ORF50 | Lytic | - | Activation of lytic cycle Stimulation of human IL-6 production Inhibition of p53 Activation of LANA-1 expression [177] |
K-bZIP /RAP | ORF K8 | Lytic | Zta (ZEBRA) in EBV | Bind to RTA protein and suppression of its transactivation Interaction with CREB binding protein Stimulation of p53 and p21 and promotion of cell cycle arrest |
v-IL-6 | ORF K2 | Lytic | IL-6 | Inhibition of apoptosis Interaction with cellular cycle Activation of JAK-STAT, MAPK-ERK and PI3-AKT pathways => Cell survival, and pro-inflammatory and pro-angiogenic environment Functional modulation of B cell by promoting CSR [183] |
v-GPCR | ORF 74 | Lytic | IL8 receptor, CXCR2 | Interaction with MAPKs, PI3K-AKT and NF-kB pathways Cell transformation Stimulation of angiogenesis |
v-bcl-2 | ORF 16 | Lytic | Bcl-2 | Inhibition of apoptosis |
K1 (KIST) | ORF K1 | Lytic | STP in SaHV | Inhibition of NF-kB pathway Cell survival by activating PI3K-AKT pathway Immune escape by the ITAM motif |
v-IRF1 | ORF K9 | Lytic | IRF1 | Inhibition of NF-kB pathway Cell proliferation Inhibition of genes expression induced by INF |
K14 | ORF K14 | Lytic | - | Inhibition of NF-kB pathway |
PAN RNA | ORF K7 | Lytic | - | LANA-1 sequestration [50] Recruitment of histone demethylase to the viral chromosome [184] Generated circRNA potentially involved in early infection [24] |
v-MIP-1 v-MIP-2 v-MIP-3 | ORF K6 ORF K4 ORF K4.1 | Lytic | MIP-1alpha - MIP-1béta | Stimulation of angiogenesis Inhibition of naïve and active human NK cells [185] |
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Jary, A.; Veyri, M.; Gothland, A.; Leducq, V.; Calvez, V.; Marcelin, A.-G. Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma. Cancers 2021, 13, 6208. https://doi.org/10.3390/cancers13246208
Jary A, Veyri M, Gothland A, Leducq V, Calvez V, Marcelin A-G. Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma. Cancers. 2021; 13(24):6208. https://doi.org/10.3390/cancers13246208
Chicago/Turabian StyleJary, Aude, Marianne Veyri, Adélie Gothland, Valentin Leducq, Vincent Calvez, and Anne-Geneviève Marcelin. 2021. "Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma" Cancers 13, no. 24: 6208. https://doi.org/10.3390/cancers13246208