Капоси саркомасымен байланысты герпес вирусы және оның зерттелуі

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, HHV 8 associated multicentric Castleman's disease and KSHV inflammatory cytokine syndrome. Even after many years since the discovery of KSHV/HHV8, there is no known cure for KSHV associated tumorigenesis.

In 1872, Moritz Kaposi described a blood vessel tumor (originally called "idiopathic multiple pigmented sarcoma of the skin") that has since been eponymously named Kaposi's sarcoma (KS). KS was at first thought to be an uncommon tumor of Jewish and Mediterranean populations until it was later determined to be extremely common throughout sub Saharan African populations. This led to the first suggestions in the 1950s that this tumor might be caused by a virus. With the onset of the AIDS epidemic in the early 1980s, there was a sudden resurgence of KS affecting AIDS patients, with up to 50% of reported AIDS patients having this tumor—an extraordinary rate of cancer predisposition. Careful analysis of epidemiologic data by Valerie Beral, Thomas Peterman and Harold Jaffe, 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. As early as 1984, scientists reported seeing herpesvirus like structures in KS tumors examined under electron microscopy. Scientists had been searching for the agent causing KS, and over 20 agents were proposed as the possible cause, including cytomegalovirus and HIV itself. 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. Chang and Moore used representational difference analysis, or RDA, to find KSHV by comparing KS tumor tissue from an AIDS patient to his own unaffected tissue. The idea behind this experiment was that if a virus causes KS, the genomic DNA in the two samples should be precisely identical except for DNA belonging to the virus. In their initial RDA experiment, they isolated two small DNA fragments that represented less than 1% of the actual viral genome. These fragments were similar (but still distinct from) the known herpevirus sequences, indicating the presence of a new virus. Starting from these fragments, this research team was then able to sequence the entire genome of the virus less than two years later. 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. The virus is now known to be a widespread infection of people living in sub Saharan Africa; intermediate levels of infection occur in Mediterranean populations (including Lebanon, Saudi Arabia, Italy, and Greece) and low levels of infection occur in most Northern European and North American populations. Gay and bisexual men are more susceptible to infection (through still unknown routes of sexual transmission) whereas the virus is transmitted through non sexual routes in developing countries.

It was discovered in 2020 that infection with the SARS CoV 2 virus, the virus which causes COVID 19, may induce the lytic reactivation of KSHV in the human body, causing the herpes virus to cease latency and begin the formation of cancerous cells. 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."

In the 1970s, the global prevalence rate for HHV 8 was 2 to 10%. The seroprevalence of HHV 8 varies significantly geographically and infection rates in northern European, southeast Asian, and Caribbean countries are between 2 4%, in Mediterranean countries at approximately 10%, and in sub Saharan African countries at approximately 40%. In South America, infection rates are low in general but are high among Amerindians. 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. Although seroprevalence has been consistently shown to increase with age in a linear manner, countries with high infection rates may see higher seroprevalence in younger age groups. Educational level has shown an inverse correlation with infection rates. In countries with low seroprevalence, HHV 8 is primarily limited to AIDS and KS patients. In countries with high seroprevalence, infection is frequent in childhood, indicating a likely mother to child transmission by saliva. In a Zambian survey, all children with KS had mothers who were positive for HHV 8, whereas not all children whose mothers had KS were HHV 8 positive. In another Zambian survey, 13.8% of children were seropositive for HHV 8 by age 4. Seroprevalence has not been shown to vary significantly because of gender or marital status. the most recent common ancestor for viruses isolated in Xinjiang was 2037 years (95% highest probability density 1843–2229 years) ago. Given the historical links between the Mediterranean and Xinjiang during the Roman period it seems likely that this virus was introduced to Xinjiang along the Silk Road. The mutation rate was estimated to be substitutions per site per year (95% highest probability density to ). However, the global distribution of different genotypes of KSHV and the potential transmission path need further studies. Typing of isolates is based on the variable K1 membrane protein. Six types are recognised (A–F).

Since persons infected with KSHV will asymptomatically give the virus, caution should be used by sex partners in having unprotected sex and activities where saliva might be shared during sexual activity. Prudent advice is to use condoms when needed and avoid deep kissing with partners with KSHV and HIV infections or whose status is unknown.

Kaposi's sarcoma is usually a localized tumor that can be treated either surgically or through local irradiation. Chemotherapy with drugs such as liposomal anthracyclines or paclitaxel may be used, particularly for invasive disease. Antiviral drugs, such as ganciclovir, that target the replication of herpesviruses such as KSHV have been used to successfully prevent development of Kaposi's sarcoma, although once the tumor develops these drugs are of little or no use. For patients with AIDS KS, the most effective therapy is highly active antiretroviral therapy to reduce HIV infection. 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. One challenge is overexpression inhibitory of target cell repress immune. Under longtime inflammation stimulation, the target cell becomes unable to respond, which leads to an exhausted phenotype. The activation immunotherapies can revive and enhance immune cell function. 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. There is high PD 1 expression in NK cells from KS HIV patients and cause exhausted phenotype. The anti PD 1 antibody, (nivolumab or pembrolizumab), demonstrated a significant antitumor effect. Nivolumab is currently an ongoing phase I clinical trial, and Pembrolizumab has shown its function in treatment for HIV and KS patients in phase I and is in a phase II trial for treatment. A thalidomide analog medicine – Pomalidomide was also granted by the FDA in 2011. Pomalidomide was shown to recover the expression of MHC 1, which help cell display intracellular proteins to cytotoxic T cells, and it also can repress the expression of PD L1 and increase the CD8+ T cell killing.