Antibody vs. HIV in a clash of evolutionary titans

Abstract

HIV has evolved many strategies to avoid neutralizing antibody responses, particularly to conserved regions on the external glycoprotein spikes of the virus. Nevertheless, a small number of antibodies have been evolved by the human immune system to recognize conserved parts of the glycoproteins, and therefore, have broadly neutralizing cross-strain activities. These antibodies constitute important tools in the quest to design immunogens that can elicit broadly neutralizing antibodies in humans and hence contribute to an effective HIV vaccine. Crystallographic analyses of the antibodies, in many cases in an antigen-complexed form, have revealed novel and, in some instances, remarkable structural adaptations to attain virus recognition. Antibodies, like HIV, can evolve relatively rapidly through mutation and selection. It seems that the structures of these broadly neutralizing antibodies bear witness to a heroic struggle between two titans of rapid evolution.

A Cryptic Polyreactive Antibody Recognizes Distinct Clades of HIV-1 Glycoprotein 120 by an Identical Binding Mechanism

“…gp120 is a subunit of the HIV envelope protein complex that is responsible for virus attachment to host cells and thus represents an important target for neutralizing antibody responses (13)(14)(15). The enormous sequence heterogeneity of gp120 allows the virus to subvert the neutralizing antibody response (13,(15)(16)(17). After prolonged infection, however, some patients mount antibody responses that efficiently neutralize many different variants of HIV-1 (18 -21).…”

Prey evolution on the time scale of predator–prey dynamics revealed by allele-specific quantitative PCR

“…For example, genetic variation in a prey population can permit evolution that radically alters predator-prey dynamics (1,2), evolution in environmentally threatened populations can affect population recovery (3), and rapid evolution is now seen as a critical component shaping disease dynamics (e.g., in HIV, refs. [4][5][6][7]. Each of these discoveries was to some extent unexpected because, despite a growing number of examples of rapid evolution (8)(9)(10)(11), the default expectation has often continued to be that ecological and evolutionary dynamics occur on different time scales (12,13).…”

The good and evil of complement activation in HIV-1 infection

“…[54][55][56][57][58][59][60] Among these nAbs, 2G12, 2F5 and 4E10 are three of the most broadly used Abs cloned from HIV-1-infected patients. 54,55,57,58,[61][62][63][64] 2G12 recognizes a unique mannosedependent epitope within gp120, 55,61,[65][66][67] while binding sites of 2F5 and 4E10 lie within a well-defined region of the membrane-proximal external region of gp41. 54,57,58,60,68 Passive immunization with a cocktail of these three human monoclonal Abs was effective in animal models, i.e., it conferred protection against intravenous, intravaginal or oral challenge with simian human immunodeficiency virus (a monkey HIV-1 analog) in rhesus macaques.…”