%0 Journal Article
%T A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement
%A Leili Jia
%A Yuanyong Xu
%A Chuanfu Zhang
%A Yong Wang
%A Huihui Chong
%A Shaofu Qiu
%A Ligui Wang
%A Yanwei Zhong
%A Weijing Liu
%A Yansong Sun
%A Fei Qiao
%A Stephen Tomlinson
%A Hongbin Song
%A Yusen Zhou
%A Yuxian He
%J Virology Journal
%D 2010
%I BioMed Central
%R 10.1186/1743-422x-7-142
%X Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively) linked to a complement-activating human IgG1 Fc domain ((anti-gp120 กม anti-C3d)-Fc), can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV.Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 กม anti-C3d)-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of (anti-gp120 กม anti-C3d)-Fc lysis of HIV compared to untreated virus.The targeted complement activator, (anti-gp120 กม anti-C3d)-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.The human immunodeficiency virus (HIV) causes severe immune deficiency in humans and over 7,000 people are infected everyday [1]. The key to resistance to HIV infection and disease progression resides within the host immune system that consists of two major defense pathways: innate and adaptive immunity [2]. There is a growing recognition that the complement system contributes to HIV replication and pathogenesis [3,4]. In fact, as a first line of defense against pathogenic microorganisms and a mediator between the innate and adaptive immune responses, the complement system is a particular focus of these immune-evasion strategies [4-6]. In human plasma, HIV immediate
%U http://www.virologyj.com/content/7/1/142