Lectins as Promising Therapeutics for the Prevention and Treatment of HIV and Other Potential Coinfections

Mazalovska, Milena; Kouokam, J. Calvin

Lectins engage in nonenzymatic and noncovalent, but highly specific, interactions with carbohydrates, binding sugar moieties and oligosaccharides, for example, oligomannose N-linked glycans (NLG) displayed on the viral envelope glycoproteins. Such interactions have important biological effects, and lectins have been widely assessed for their potential activities against enveloped viruses as described above. However, among human pathogens, surface exposed oligosaccharides are not limited to viral envelopes. Indeed, it is widely admitted that glycosylation represents the most important cotranslational and posttranslational modification of proteins in virtually all living organisms [11, 88] . Thus, lectins could theoretically interfere with sugar moieties of glycans displayed on many cell types, including bacteria, yeasts, and parasites. It is known that the incidence of HIV/AIDS is exacerbated in individuals infected with other sexually transmitted pathogens. Both ulcerative (candidiasis, chancroid, syphilis, genital herpes, and genital warts) and inflammatory (chlamydia, gonorrhea, and trichomoniasis) sexually transmitted diseases (STDs) have been shown to increase susceptibility to HIV infection [89] [90] [91] . In addition, STDs increase virus shedding in HIV infected patients, rendering them even more infectious [91] . Conversely, in an immune system heavily altered by AIDS, the etiologic agents of STDs have an easier path to cause illness. Therefore, it is reasonable to assume that the biological and epidemiological synergies between HIV and STDs can also promote HIV superinfection, that is, reinfection of an individual who already has an established infection with a heterologous HIV strain (Figure 1 ). Although the amplitude of HIV superinfection is not entirely known, this complication certainly affects the magnitude of global HIV diversity, which is driven in large part by recombination between viruses [92] . Apart from these sexually transmissible pathogens, other microbes might also take advantage of the weakened immune system of HIV infected patients and cause various diseases and/or further alter the immune system. Considering the above-mentioned synergy between HIV infection and STDs, in addition to the possibility of superinfection in seropositive individuals, there is an urgent need for novel anti-HIV agents, which would simultaneously target other pathogens. In the case of sexually transmitted organisms, a socioepidemiological rationale was recently proposed for the development of multipurpose prevention technologies [93] , since current HIV prevention methods fall well short of needs. This would help tackle both AIDS and other STDs and likely improve the immune system of the affected patients.