Anti-HSV type 2 Polyclonal antibody

We show that genital infection with neurotropic HSV type 2 (HSV-2) induced a significant increase of the neuropeptide substance P (SP) within the genital tract of mice. SP was shown to weakly interfere with the HSV-2 replication. Furthermore, lack of SP signaling through the use of mice deficient in the SP receptor, neurokinin 1 receptor (NK1R), revealed an important role for SP in the innate defense against HSV-2. NK1R-deficient mice had significantly enhanced levels of HSV-2 in the genital tract and in the CNS following infection and a significantly accelerated disease progression, which was associated with an impaired NK cell activity locally in the vagina. Lack of NK1R signaling did, however, not impair the animals' ability to mount a protective immune response to HSV-2 following vaccination with an attenuated virus. Both NK1R(+/+) and NK1R(-/-) mice developed strong HSV2-specific Thl T cell responses following vaccination. No genital viral replication was observed in either vaccinated NKIR-deficient or NK1R(+/+) control animals following a genital HSV-2 challenge, and all of these animals survived without any symptoms of disease. In conclusion, the present results indicate that SP and NK1R signaling contributes to the innate resistance against HSV-2 infection in mice.

The genomic location and DNA sequence of the simian herpesvirus SA8 gene encoding a homologue of the HSV1 gB glycoprotein was determined. Using a cloned gB gene of herpes simplex virus type 1 (HSV1) as probe in Southern blot hybridizations, the SA8 gB gene was localized to a 10-kbp Kpnl fragment mapping in the unique long part of the genome. A 2.8 kbp, 68.4% GC segment of this fragment was sequenced. It contained a 2649 nucleotide ORF possibly encoding a 98.4kDa polypeptide. The predicted amino acid sequence of the SA8 gB polypeptide is 78.4% and 78.9% identical to the sequence of the HSV1 and HSV2 gBs, respectively, and was 88.4% similar or identical to both HSV gB sequences. Structural characteristics predicted for the SA8 gB polypeptide were very similar to those of HSV1 gB. These included a hydrophobic signal sequence of 29 amino acids, conservation of all 10 cysteine residues and 5 of 6 potential N-linked glycosylation sites present in the HSV1 gB, a triple hydrophobic transmembrane domain, and a highly charged cytoplasmic tail region. Both hierarchical cluster analysis and phylogenetic analysis of sequences for gB polypeptides of 12 different herpesviruses demonstrated that the gB glycoprotein of SA8 is most closely related to the HSV gB glycoproteins. Comparison of these closely related gB sequences identified four regions in which non-conservative amino acid substitutions were clustered. Localized regions of the gB polypeptide were identified which are likely to be associated with the conserved structure/function of the polypeptide.