PREFACE
The Human Immunodeficiency Virus (HIV) infection represents one of the biggest challenges faced by the scientific community in recent years. HIV was discovered in the early ‘80s and has caused one of the most dramatic epidemics (known as the Acquired ImmunoDeficiency Syndrome, AIDS) of the last (and current) century.
Very extensive knowledge has been accumulated on the virus as well as on the deleterious effect of viral proteins for the host, leading to efficient therapies controlling viral replication. However, in the face of the great advances in antiretroviral therapy scientists and physicians still do not have effective countermeasures for preventing infection with microbicides or vaccines and for eradicating the infection in those who have already acquired HIV, while the selection of drug-resistant strains, as well as side-effects, represents frequent problems for those under antiretroviral regimens.The earliest defense against microbial infections is represented by the responses of the innate immune system that is finely tuned by different cellular types and several soluble factors. Related to HIV infection, soluble molecules of the innate immune system target multiple steps in the virus life cycle, sometimes in favor of the host and sometimes of the virus, for example for cytokines and the complement system. On the other hand, it has been clearly demonstrated that the potency of early immune responses profoundly regulates the levels of HIV replication and spreading and, overall, the speed of disease progression towards AIDS. Findings obtained with clinical trials based on α1-antitrypsin or IL-2 therapy in HIV individuals have clearly shown that strategies aimed at the manipulation of the immune system responses are feasible ways to enhance the control of virus replication, for example by boosting the ability of CD8+ T cells to release soluble, non-lytic anti-viral factors (CAF). Therefore, better characterization of the interactions between soluble factors mediating innate immune system responses and HIV might lead to the design of immunological compounds boosting the innate immune system against HIV.
Most of these soluble mediators owing to anti-viral activity are independent of co-receptor usage, drug-resistance mutations, thus widening their therapeutic window in all stages of disease. In addition, a better comprehension of anti-viral activities delivered by innate immune response might turn fundamental for the design of anti-HIV vaccines.Common denominator of all chapters described in this e-book is the mutual interaction between innate immunity and HIV infection, a topic that has been investigated from the late '80s. Different authors describe different soluble factors responsible for the regulation of HIV infection and replication in various cell types and model systems of infection.
Therefore, this e-book provides a very detailed description about the role of innate immune responses regulating HIV replication according to the studies of several international experts. I do hope that this book will be a key reference text for a wide range of scientists, such as graduate students, for which it represents a good starting point, as well as for investigators in general, for whom it may represent a collection of the state of the art of 20 years of HIV research.
Massimo Alfano, Ph.D.