HIV-1 Host Resistance [B23.8]
Dr. rer. nat. Christoph Marschall, Dipl.-Biol. Christine Schack,
Dipl.-Biol. Christina Sofeso
The human immunodeficiency virus type 1 (HIV-1) leads to AIDS usually 10-15 years after infection. AIDS is a severe disorder of the immune system which results in nearly uncontrollable infections with microorganisms or in malignant tumor diseases due to loss of function of the T4 helper cells. According to the WHO, the estimated global number of HIV-infected patients, who could potentially transmit the disease, is 40 million.
The HI virus enters the host cell through interaction with its main receptor CD4 and (depending on the cell) one of the two co-receptors CCR5 and CXCR4. Both co-receptors are membrane-bound chemokine receptors which are down-regulated from the cell surface after binding of a ligand (SDF-1, MIP-1 or RANTES). CCR2 is another chemokine receptor, whose aberrant form binds to CCR5 which also leads to down-regulation. Through this process, the reception of the virus is reduced. Genetic variants (polymorphisms) both in the chemokine receptors and in the chemokines themselves have been associated with individual variations regarding susceptibility towards HIV-1 infection and therapy (see also chapter Pharmacogenetics).
The HLA system seems to play a role in the progression of AIDS as well. Patients who carry the HLA-B*35 subtypes B*35:02/35:03/35:04/53:01 (also known as B*35-PX allele) exhibit a more severe course of the disease than patients who carry the B*35:01 type (also known as B*35 PY allele). The presentation of virus epitopes via B35-PX and the immunologic synapse formed in this process may lead to a more effective transmission of the virus to activated T cells or to a less effective fight against infected cells. In carriers of the HLA-B*57:01/57:03 subtype, the course of the HIV infection is slower; most likely due to effective presentation of virus epitopes. The B*57:01 allele is furthermore significant for treatment, since carriers of this subtype frequently exhibit hypersensibility towards the nucleoside analogue Abacavir. For this reason, HLA typing prior to treatment should be considered (see also Pharmacogenetics).