[2] This virus causes Kaposi's sarcoma, a cancer commonly occurring in AIDS patients,[3] as well as primary effusion lymphoma,[4] HHV-8-associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome.

[7] Careful analysis of epidemiologic data by Valerie Beral, Thomas Peterman and Harold Jaffe,[8] led these investigators to propose that KS is caused by an unknown sexually transmitted virus that rarely causes tumors unless the host becomes immunosuppressed, as in AIDS.

[citation needed] As early as 1984, scientists reported seeing herpesvirus-like structures in KS tumors examined under electron microscopy.

The pathogen was ultimately identified in 1994 by Yuan Chang and Patrick S. Moore, a wife and husband team at Columbia University, through the isolation of DNA fragments from a herpesvirus found in a KS tumor in an AIDS patient.

In their initial RDA experiment, they isolated two small DNA fragments that represented less than 1% of the actual viral genome.

[citation needed] The discovery of this herpesvirus sparked considerable controversy and scientific in-fighting until sufficient data had been collected to show that indeed KSHV was the causative agent of Kaposi's sarcoma.

[citation needed] KSHV is a herpesvirus, and is a large double-stranded DNA virus with a protein covering that packages its nucleic acids, called the capsid, which is then surrounded by an amorphous protein layer called the tegument, and finally enclosed in a lipid envelope derived in part from the cell membrane.

[citation needed] Once the virus newly infects a cell, the lipid membrane is shed and the virion travels to the nucleus.

The viral genome is released where it circularizes into an episome through a poorly understood process that appears to involve homologous recombination of the terminal repeats.

[20] Additionally, it has been shown that vFLIP and vCyclin interfere with the TGF-β signaling pathway indirectly by inducing the oncogenic host mir17-92 cluster.

When cell signaling conditions activate the generation of RTA, it in turn activates synthesis of a stereotypic cascade of secondary and tertiary viral proteins that ultimately make components of the virus capsid and also the DNA synthesis enzymes required to replicate the virus genome.

As each unit genome is replicated, it is cut within the terminal repeat region, and then packaged into a virus particle (virion).

Thus, whereas KSHV genome is circular in the nucleus of latently infected cells, it is packaged into infectious viruses as a linear molecule.

Further, it was discovered that some medications used to treat the infection with SARS-CoV-2, namely Nafamostat and Azithromycin, ended up promoting the production of mature virions, "... potentially inducing KSHV lytic reactivation.

Kaposi's sarcoma occurs when someone who has been infected with KSHV becomes immunocompromised due to AIDS, medical treatment, or, very rarely, aging.

[33] Even within individual countries, significant variation can be observed across different regions, with infection rates of about 19.2% in Xinjiang compared to about 9.5% in Hubei, China.

[49] AIDS patients receiving adequate anti-HIV treatment may have up to a 90% reduction in Kaposi's sarcoma occurrence.

Although KSHV affects the host immune system, there is ample chance for clinical intervention to recover this change.

Comparing to other immunotherapies, therapies targeting the anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has been a great success.

Because of KSHV infection, the monocytes increase the expression of PD-1, which is an inhibitory molecule, and cause immune escape in many tumor types.

PAN, polyadenylated nuclear RNA – non–coding linear and circular RNAs miRNAs (mirKs) – viral microRNAs expressed during latency to regulate proliferation and cell death K1 – involved in oncogenesis K2 – Interleukin 6 homolog, Q2HRC7 K3 and K5 – ubiquitin E3 ligases – regulates antigen presentation K4 – vCCL2 – chemokine K4.1 – vCCL3 – chemokine K8 – transcriptional repressor – modulates chromatin K8.1 – envelope glycoprotein K9 – vIRF1, viral interferon regulatory factor 1 K10 – vIRF4.

K10.5 – vIRF3 (initially designated LANA2), is expressed during latency in PEL cell lines, but is also a bona fide lytic factor, like all of the vIRFs.