Candidate topical microbicides bind herpes simplex virus glycoprotein B and prevent viral entry and cell-to-cell

Procapsids are more rounded and porous than angular A-, B-, and C-capsids (64), contain unprocessed internal scaffold, and are unstable at low temperatures (36, 39,52). Previous studies demonstrated that several viruses, including HSV, depended on cellular proteasome activity to facilitate their postentry events, such as viral gene expression, replication, and immune evasion (19). It has been reported that UL47 plays an important role in viral replication and pathogenicity, based on studies showing that recombinant UL47 mutant viruses have reduced growth and reduced pathogenicity in cell cultures and/or a mouse model (20, 21). Immunocytochemical staining was performed on paraffin-embedded sections according to the avidin-biotin-peroxidase method.23 Briefly, the sections were deparaffinized, rehydrated, and treated with 3% hydrogen peroxidase for 10 minutes to block endogenous peroxidase activity. In the present report, we readdress the role of autoimmunity and molecular mimicry between IgG2a and UL6 peptides in HSK pathogenesis by using a mouse model involving different mice strains on the same genetic background as used in the previous reports and a strain of HSV type 1 (HSV-1) (strain RE) usually used for the induction of HSK lesions. In the present study, expanding on comparative analysis of nuclear components, we examine some of the major nuclear pore constituents in infected versus uninfected cells and undertake a functional analysis of nuclear gating in live infected cells. The protease not only cleaves itself to release the N-terminal catalytic domain (VP24) but also cleaves the precursor scaffold proteins (pre-VP22a; pUL26.5) to release them from VP5.

Although many of the details of viral entry remain poorly understood, it is widely accepted that fusion requires four of the virion glycoproteins: gB, gD, and the heterodimer gH-gL (reviewed in 28 and 29). It is a highly selective antiviral agent because it is specifically phosphorylated by viral thymidine kinase in infected cells (10, 13). However, studies of the interactions between HSV and DCs have yielded conflicting results. CD8+ T cells infiltrate the TG during acute HSV-1 infection, with peak accumulation occurring coincident with the elimination of replicating virus and the establishment of latency (9, 35). The activation of conventional PKCs and novel PKCs also involves recruitment to cellular membranes, whereas atypical PKC activation does not (4, 25). This might circumvent the limited anatomic spread observed with the inoculation of replication-defective vectors and/or producer cells into human tumors (43, 47). In contrast, SPs and SAMMA exhibit little or no cytotoxicity in vitro and are active against HIV, HSV, Neisseria gonorrhoeae, Chlamydia trachomatis, and human papillomavirus (Table 1) (2, 3, 12).

An essential role for rafts has been described for the initiation of Fas-mediated cell death signaling (32). Beginning at 3 to 5 h postinfection (hpi), HSV-1 induced a strong and persistent nuclear translocation, increased p50/p65-dependent DNA binding activity as measured by electrophoretic mobility shift assay (EMSA), and induced activation of a 3XNFκB-luciferase reporter. This may not be the complete list of references from this article. Links to PubMed are also available for Selected References. gB became favored as the fusion protein when three-dimensional structures were determined. Historically Herpes simplex 1 has not been known to cause genital herpes, but this is changing, especially among sexually active young people. About one third of the human population suffers from recurrent infection of skin and other tissues occurring mostly at irregular intervals.

Individual polypeptides that contained single insertions of 2 to 28 amino acids throughout the external domain were not recognized or were recognized poorly by antibodies specific for sites II and III, whereas no insertion affected antibody recognition of sites I and IV. Full text Full text is available as a scanned copy of the original print version. (i) Only two mutants contained mutations at a site which did not overlap with the previously reported mutation. The carboxyl-terminal half of the protein consists of a regular tripeptide repeat of the sequence RXP and constitutes a completely novel RNA-binding domain. Although several of the polymers have advanced to clinical trials, the spectrum and mechanism of anti-HSV activity and the effects on soluble of mediators of inflammation have not been evaluated. Three peptides (gB94, gB122, and gB131) with 50% effective concentrations (EC(50)s) below 20 microM were selected for further studies. The greater than expected enhancement of virus production of C1300 cell cultures receiving increasing MOI of HSV was probably not due to improved virus adsorption, nor influenced by non-virus factors in the virus inoculum stimulatory for HSV replication.

Both gB and the nonessential gC interact with cell surface heparan sulfate proteoglycan (HSPG), promoting viral attachment. We describe an HSV-2/1 cross-reactive cytotoxic T-cell (CTL) epitope that is processed in a TAP1-independent manner in vivo following immunization of TAP1-/- mice with naked DNA or a recombinant vaccinia virus. Internalization of virus following preincubation at 4 degrees C and temperature shift to 37 degrees C was normally preceded by a 5 to 8 min lag period and was complete within 20 to 30 min.

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