Human leukocyte antigen polymorphisms and Kaposi's sarcoma‐associated herpesvirus infection outcomes: A call for deeper exploration

Abstract

Host genetic background may influence the immunity to resist viral infection. As the most polymorphic loci in the entire human genome, the human leukocyte antigen (HLA) system plays an important role in innate and adaptive immune responses to many invading pathogens. Studies have shown that an association might exist between HLA polymorphisms and susceptibility to Kaposi's sarcoma‐associated herpesvirus (KSHV) infection and associated diseases. However, discrepant conclusions were reached among different subjects with different detection methods. Therefore, it is now urgent to summarize current results and figure out the achievements and deficiencies of the existing research for the reference to future studies. A better understanding about the role of HLA polymorphisms in KSHV infection outcome would enable us to elucidate the pathways through which the virus evades the host defense system and improve strategies for the prevention and treatment of KSHV infection.

Kinetics of Abacavir-Induced Remodelling of the Major Histocompatibility Complex Class I Peptide Repertoire

“…In humans, classical MHC I molecules are co-dominantly expressed from three gene loci known as Human Leukocyte Antigen (HLA)-A, -B and -C. In addition to expected genetic associations between different HLA-A, B, and C allotypes and susceptibility to various infectious agents (5)(6)(7)(8)(9)(10) or autoimmune disorders (11)(12)(13)(14)(15)(16)(17)(18), quite profound associations have also been made between these genes and drug hypersensitivity reactions (19). Some of these HLA associations represent the strongest of any HLA-linked responses with odds ratios (>500) for distinct hypersensitivity reactions towards the anti-epileptic carbamazepine and HLA-B*15:02, the anti-hyperuricaemic allopurinol and HLA-B*58:01, and the anti-retroviral abacavir and HLA-B*57:01 (20)(21)(22).…”

Value of first‐line surgical treatment for classic Kaposi sarcoma and potential use of checkpoint inhibitors

“…Classic Kaposi sarcoma is a neoplasm of lymphatic endothelial cells that requires infection with human herpes virus type 8 (HHV-8) and other co-factors for its development. Association with HLA-DR5 has been suggested [1]. The disease is particularly common in older men from Southeast Europe and the Middle East.…”

Inhibitory KIR2DL2 Receptor and HHV-8 in Classic or Endemic Kaposi Sarcoma

“…In this case, the virus remains latent within cells and clinically silent. On the other hand, since it has developed a variety of mechanisms to evade the host immune system [30,15], HHV8 may lead to the proliferation of infected cells, up to cancer development [19]. The kinetics of virus-associated disease progression depends on the balance of power between host immune defenses and the virus [26].…”

“…In keeping with this, the risk for KS is greatly increased with concomitant human immunode ciency virus (HIV) infection and also substantially increased in the case of chronic use of corticosteroids and immunosuppressive treatments [21]. However, it is not currently understood in detail which components of the human immune response are essential for this pathophysiological process [2,19].…”