Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) Lifecycle: An Overview of Latency, Lytic Replication, and KSHV-Associated Diseases
Abstract
:1. Introduction
2. Virion Structure, Viral Genome, and KSHV Entry
2.1. Virion Structure
2.2. KSHV Genome
2.3. KSHV Entry
3. Latency: Quiescent Phase of the Lifecycle
3.1. Establishment of Latency
3.2. KSHV Latency-Associated Nuclear Antigen (LANA)
3.3. KSHV Viral Cyclin (vCyclin)
3.4. KSHV Viral FLICE-Inhibitory Protein (vFLIP)
3.5. KSHV Kaposins
3.6. LANA2/Viral Interferon Regulatory Factor 3 (vIRF3)
3.7. microRNAs: Tiny Regulators, Big Impact
4. KSHV Signaling Proteins
4.1. KSHV K1
4.2. KSHV K2/vIL-6
4.3. KSHV K15
5. Lytic Replication
5.1. KSHV RTA: Master Regulator of the Lytic Switch
5.2. KSHV K8
5.3. KSHV ORF57, Delayed Early Protein
5.4. Viral DNA Replication and Late Gene Expression
6. Modulation of Cell Pathways by Lytic Proteins
6.1. K3 and K5: Modulators of Immune Recognition
6.2. KSHV IRFs: v-IRF1, 2, and 4
6.3. Viral Chemokines: vCCL1, 2, and 3
6.4. Lytic Signaling Proteins: vGPCR and vPK
6.5. KSHV vBcl-2
6.6. Contribution of Lytic Proteins to KSHV Pathogenesis
7. KSHV-Associated Diseases
7.1. Kaposi Sarcoma (KS)
7.2. Primary Effusion Lymphoma (PEL)
7.3. Multicentric Castleman Disease (MCD)
7.4. KSHV Inflammatory Cytokine Syndrome (KICS)
8. Therapeutics
8.1. Current Therapeutic Approaches
Name | Type | Target | Disease | Reference |
---|---|---|---|---|
BV | Chemotherapeutic regimen | DNA/Topoisomerase II, Microtubules | KS | [309] |
ABV | KS | |||
PLD | Topoisomerase II | KS | ||
CHOP | DNA/Topoisomerase II, Microtubules, Glucocorticoid receptor | PEL | [298] | |
EPOCH | PEL | |||
Paclitaxel | Chemotherapeutic agent | Microtubules | KS | [310] |
Ganciclovir | Antiviral drug | DNA polymerase | KS | [312,313] |
Cidofovir | PEL | [314] | ||
Siltuximab | Antibody therapy | IL-6 | MCD | [315] |
Tocilizumab | IL-6 receptor | MCD | [316] | |
Rituximab | CD-20 | MCD | [317] | |
Pembrolizumab and nivolumab | Immune checkpoint blockade therapy | PD-1 and PD-L1 | KS | [318,319] |
Nivolumab and ipilimumab | PD-1 and CTLA-4 | KS | [320] | |
Pomalidomide and lenalidomide | Immunomodulatory imide drugs (IMiDs) | Ubiquitin E3 ligase substrate adapter Cereblon | KS/PEL | [321] |
Interleukin-12 therapy | Cytokine | IL-12 | KS | [322] |
Rapamycin | Macrocyclic immunosuppressive drug | mTOR pathway | KS/PEL | [323,324] |
Azidothymidine and interferon alpha | Nucleoside analog reverse transcriptase inhibitor (NRTI) and immunomodulator | NF-κB | PEL | [309] |
Imatinib | Kinase inhibitor | Tyrosine kinase inhibitor | KS | [325] |
Bortezomib | Protease inhibitor | 26S proteasome | KS | [326] |
Bevacizumab | Antibody therapy | VEGF inhibitor | KS | [327] |
8.2. Targeted and Emerging Therapies
8.3. Future Directions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Losay, V.A.; Damania, B. Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) Lifecycle: An Overview of Latency, Lytic Replication, and KSHV-Associated Diseases. Viruses 2025, 17, 177. https://doi.org/10.3390/v17020177
Losay VA, Damania B. Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) Lifecycle: An Overview of Latency, Lytic Replication, and KSHV-Associated Diseases. Viruses. 2025; 17(2):177. https://doi.org/10.3390/v17020177
Chicago/Turabian StyleLosay, Victor A., and Blossom Damania. 2025. "Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) Lifecycle: An Overview of Latency, Lytic Replication, and KSHV-Associated Diseases" Viruses 17, no. 2: 177. https://doi.org/10.3390/v17020177
APA StyleLosay, V. A., & Damania, B. (2025). Unraveling the Kaposi Sarcoma-Associated Herpesvirus (KSHV) Lifecycle: An Overview of Latency, Lytic Replication, and KSHV-Associated Diseases. Viruses, 17(2), 177. https://doi.org/10.3390/v17020177