Tag Archives: herpes

Guest Blogger, Immunology, Vaccines

After many setbacks, cross-presentation provides new hope for a Herpes Simplex Virus 1 vaccine

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Contributed by guest blogger: Stephanie Mischell ’12

Herpes simplex virus type 1 (HSV-1) is making news due to a paper by Jing et al identifying two promising new candidate antigens for a vaccine. HSV-1 is a widespread public health issue, infecting approximately 60% of Americans and causing symptoms, most likely cold sores or genital sores but on rare occasion blindness or fatal brain damage. Furthermore, finding a vaccine for HSV-1 has proved difficult, in part because of the vital but elusive role of CD8+ T-cells in the HSV-1 immune response. Mice studies suggest that a CD8-response could facilitate memory cell formation and ameliorate chronic disease caused by HSV-1, but human blood does not have many HSV-1 specific CD8+ T-cells and very few CD8 epitopes have been identified.  Previous attempts at vaccines most recently using the HSV glycoprotein D (gD2), have focused on CD4+ T-cell specific epitopes. These attempts were unable to stimulate a CD8+ T-cell response, and the vaccine failed during clinical trials. A way to stimulate both CD4+ and CD8+ T-cell responses seems necessary to create an effective vaccine.

Jing et al’s work is significant because it harnesses properties originally used to study HSV-2 to identify HSV-1 epitopes recognized by CD8+ T-cells. An epitope, or antigenic determinant, is the part of an antigen that is recognized by the immune system; this interaction is what triggers a host immune response. Jing et al demonstrated previously that in vitro monocyte-derived dendritic cells (moDC’s), or antigen-presenting cells, can cross-present HSV-2  epitopes to create  HSV-2 specific memory T-cells. In this paper, they harnessed this cross-reactivity of moDC’s and applied it to HSV-1, stimulating and identifying HSV-1 specific CD8+ T-cells. 45 distinct CD8+ T-cell epitopes were identified. Furthermore, the genomes of host responder cells were cloned, and HSV-1 epitopes were analyzed for HLA restriction. Proteins from two genes, UL39 and UL46, were identified as most highly restricted, suggesting that they are most involved in the immunogenic response. PMBC assays confirmed these results quantitatively.

Jing et al conclude that the viral proteins coded by UL39 and UL46 are good candidate antigens for an HSV-1 vaccine because of their CD4+ and CD8+ T-cell  immunogenicity. However, they also acknowledge that their sample size is small and that subunit vaccines have not been successful vaccines for HSV-1. In fact, the large number of CD8+ T-cell   epitopes identified led the authors to conclude that a whole-virus vaccine may be more successful than subunits. Most of the failed vaccines showed similar promise until phase II or phase III of clinical trials, suggesting that the small amount of data from this study is just a start. This discovery is important but not a guaranteed vaccine.

While the identification of UL39 and UL46 are important steps in solving the public health issue posed by HSV-1, as is the identification of other CD8+ T-cell   epitopes, perhaps the most significant part of the study is the implications of their novel research methods on the study of viral vaccines. The enrichment techniques used could potentially make studying T-cell responses easier. The authors confirmed the applicability of their methods by using the same techniques to study the vaccinia virus, a microbe with a large genome of over 200 genes. This paper demonstrates a small advancement in HSV-1 research and control, but may have larger implications for this and other large viruses.

Link to original article: http://www.jci.org/articles/view/60556

Stephanie Mischell is a senior at Vassar College, majoring in biology.

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Environmental virology, Guest Blogger

Herpes-Family Viruses are Associated with Stressed Out Corals

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Contributed by guest blogger: Ian Heller ‘12

A new review out in the Journal of Experimental Marine Biology and Ecology is causing a rash of media attention regarding the presence of viruses in stressed out coral. However, this media attention, with catchy titles playing at old stigmas against herpes infection in humans, misses the true story told being uncovered in the new field of coral virology. What has the science actually shown?

Coral reefs are hotspots of biodiversity and essential components of the ocean ecosystem. Corals themselves contain an amazingly diverse assembly of different organisms. Tiny organisms like symbiotic algae, fungi bacteria, and archaea are all necessary for healthy coral. Unfortunately, coral reefs are threatened world wide due to rising sea temperatures, acidifying ocean water, and pollution in the form of sewage and fertilizer runoff. These stressors seem linked to an increased incidence of disease in coral, but what pathogens are actually making corals sick?

To investigate whether any viruses were associated with stressed coral, researchers compared the metagenomes of healthy corals and corals grown in water that was too hot, too acidic, too polluted with organic carbon (to simulate sewage stress) or too polluted with plant fertilizer nutrients. Within this “metagenome” is all of the DNA sequences from all of the different algae, bacteria, virus, etc., that are part of each sample, in this case, a coral fragment.

The first step in making such a comparison is sequencing as many of the genes as possible each sample, a feat made feasible by the increasing accessibility of gene sequencing. Next, researchers identify all of the sequences in their samples’ “library” of genes that correspond to viral genes. This means sifting through over 51,000 sequences! To figure out the identify of these sequences, the researchers use a computer algorithm known as BLAST to compared their unknown sequences with known sequences in National Center for Biotechnology Information’s public database of nucleic acid sequences. Then, to find their “viral needles” in the “metagenome haystack”, they use various computational approaches to eliminate non-viral sequences and identify viral sequences. In their results, the researchers found viral sequence from 19 different virus families. Then, when the metagenomes from healthy corals were compared to stressed corals, it was found that the stressed corals had an increased frequency of herpes-virus family sequences.

To confirm that this frequency shift actually corresponded to more herpes genes in stressed corals, the researchers used Real-Time PCR (also know as quatitative PCR) to measure the concentrations of a specific nucleic acid sequence in different corals.  The nucleic acid sequence that was focused on was a herpes virus sequence similar (62% identical) to the thymidylate synthase gene from Saimiriine herpesvirus 2. This experiment showed that indeed, stressed corals tended to have more of this gene in their metagenome than their healthy counterparts.

This study provides an excellent first step into the world of coral virology; it identifies possible candidate viruses that may be contributing to coral illness. However many more questions need to be answered to understand viruses’ role in coral health. For example, few studies have actually observed virus actively hosted by a coral, and none have yet shown that herpes-like viruses can make healthy, unstressed corals sick. The ecological role of viruses may turn out to be surprisingly complex. Some researchers have even proposed that viruses may be necessary for coral survival. Corals host symbiotic algae within their cells, in a mutualism that is a requirement for corals to survive. In order to live inside coral cells, the algae must somehow evade or suppress the corals innate immune response, just as many viruses must do. Will future studies discover a link between the algae infection and virus infection?

Links:

http://dx.doi.org/10.1016/j.jembe.2011.07.030

http://www.pnas.org/content/105/47/18413.full

Ian Heller is a senior at Vassar, majoring in biology.  He is also good at making puns, and had a hard time choosing a title for this article.  Rejected titles included: Catching herpes from coral sex, Viruses and corals: friends or anemonies?, and Virus in the O.K. Coral. 

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