Báo cáo sinh học: Prevention of genital herpes in a guinea pig model using a glycoprotein D-specific single chain antibody as a microbicide

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Prevention of genital herpes in a guinea pig model using a glycoprotein D-specific single chain antibody as a microbicide
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Báo cáo sinh học: " Prevention of genital herpes in a guinea pig model using a glycoprotein D-specific single chain antibody as a microbicide"Virology Journal BioMed Central Open AccessResearchPrevention of genital herpes in a guinea pig model using aglycoprotein D-specific single chain antibody as a microbicideJianmin Chen, Sanat K Davé and Anthony Simmons*Address: University of Texas Medical Branch, Galveston, Texas, USAEmail: Jianmin Chen - jiachen@utmb.edu; Sanat K Davé - skdave@utmb.edu; Anthony Simmons* - ansimmon@utmb.edu* Corresponding authorPublished: 23 November 2004 Received: 11 November 2004 Accepted: 23 November 2004Virology Journal 2004, 1:11 doi:10.1186/1743-422X-1-11This article is available from: http://www.virologyj.com/content/1/1/11© 2004 Chen et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Genital herpes (GH) is a recurrent sexually transmitted infection (STI) that causes significant morbidity and is also the major source of herpes simplex virus (HSV) in cases of neonatal herpes. Vaccination is a current goal which has had limited success so far in preventing GH and microbicides offer an attractive alternative. Treatment of primary disease cannot prevent establishment of latent infections and thus, cannot prevent subsequent recurrent disease. Recently, many of the molecular events leading to entry of HSV into cells have been elucidated, resulting in the description of a number of herpesvirus entry mediators (HVEMs) that interact with HSV glycoprotein D (gD) on the surface of virions. Described here is a strategy for interrupting the spread of HSV based on interfering with these interactions. The hypothesis addressed in the current report was that single chain antibody variable fragments (scFv) that interrupt associations between gD and HVEMs would not only prevent infection in vitro but could also be used as microbicides to interfere with acquisition GH. Results and Conclusions: Here we show that a scFv derived from a particular hybridoma, DL11, not only inhibits infection in vitro but also prevents development of GH in a guinea pig model when applied intravaginally in an inert vehicle. Comparison of different anti-gD single chain antibodies supported the hypothesis that the activity of DL11-scFv is based on its ability to disrupt the associations between gD and the two major receptors for HSV, nectin-1 and HveA. Further, the results predict that bacterial expression of active single chain antibodies can be optimized to manufacture inexpensively a useful microbicidal product active against HSV. sory neurons innervating initially infected skin andBackgroundGH is generally caused by HSV type 2 (HSV-2), though mucous membranes [2,3]. The significance of latency isHSV type 1 (HSV-1) is increasingly recognized as a signif- that it is a reservoir of infection that can periodically reac-icant cause of primary infections [1]. Throughout the last tivate, causing virus to travel down nerve fibers to skin orfew decades there were substantial advances in under- mucous membranes in the dermatome of primary infec-standing the epidemiology of genital HSV infections. Pri- tion. This may be manifest clinically as recurrent GH ormary infection is almost always self-limited but on more frequently, causes unrecognized shedding of infec-healing virus is not eliminated from the host but rather, tious HSV [4-7] which despite being unrecognized isviral genomes remain in a latent (dormant) state in sen- responsible for the majority of new HSV-2 infections [8]. Page 1 of 10 (page number not for citation purposes)Virology Journal 2004, 1:11 http://www.virologyj.com/content/1/1/11The epidemiology is further complicated by the fact that 1A 1Bmany primary infections are asymptomatic or unrecog-nized, which has the important implication that the firstclinical presentation of GH, often referred to as the initialepisode, may be caused by a recurrence of a prior asymp- 369tomatic primary infection [9].In the latter half of the 20th century, there were greatstrides in antiviral therapy for GH but unfortunately, treat- N 1ing primary disease does not prevent establishment ofinfection [10 ...