Genetic Factors that Influence HIV Infection: The Role of the Major Histocompatibility Complex System

Abstract

The HIV epidemic continues to be a major world-wide health and human problem as reflected in the AIDS epidemic updates from the World Health Organization (WHO). Highly active antiretroviral therapy (HAART) has improved health management, especially in developed countries, since it was first introduced in the mid-1990s. However, access to antiretroviral therapy in developing countries has been limited. Developing an effective vaccine is an on-going mission, the success of which depends on understanding key aspects of the immune response to HIV. Hence, studying the genetic components of the immune response to the HIV virus is essential. The existence of genetic factors that modulate immune response to infectious diseases was described more than 10 years ago (Hill, 1998). We recommend various recent and extensive reviews that have focused on the immunobiology of HIV infection (Tripathi and Agrawal, 2007), the immune response to HIV (Chakrabarti and Simon, 2010; Miyazawa, et al. 2008) and specifically the innate response (Borrow and Bhardwaj 2008). Innate and adaptive immune responses play a decisive role during the initial stages of HIV infection and will also affect the progression of the disease. Definitive evidence that host genetics plays a role in the immune response to HIV is the fact that HIV-1 infection does not always progress to AIDS. A small percentage (less than 0.2%) of HIV-1 sero-positive patients is able to control the infection, meaning that they can maintain a viral load of fewer than 50 copies of HIV-1 RNA per ml over 10 years. These patients have been given different names: HIV controllers, HIV elite controllers, long-term non-progressors (LTNPs) or natural virus suppressors (Chakrabarti and Simon, 2010). This chapter focuses on the influence exerted on HIV infection by the human major histocompatibility complex (MHC) system, also known as the human leukocyte antigen (HLA) system. The effect of the MHC system on HIV infection is crucial for development of an effective vaccine. We recommend several reviews on this subject that complement the present monograph (Carrington and O'Brien, 2003; Stephens, 2005; Miyazawa et al. 2008; Kaur and Mehra, 2009; Singh and Spector, 2009). In this chapter, we will first describe the most important and relevant characteristics of the MHC, then we will review the recent