Achieving a cure for HSV infections has to be the ultimate objective. However, first we need to define what would constitute a cure.
Removing viral material from the sensory ganglia is, putting it mildly, a tall order. The viral genetic material which is exchanged between neuronal cells contains no proteins or other markers by which the immune system recognises infection. Genetic intervention, for example using a carrier virus to displace or disrupt HSV, is medically a long way off. Such an approach also involves the risk of damaging neuronal cells, which could lead to long-term loss of sensation.
A much more realistic goal is the extended, or even permanent, suppression of peripheral reactivation – outbreaks at the skin. Such a cure, if it does emerge, is unlikely to be a perfect remedy which works all the time. More typical is that a realisation is reached that a certain method resolves a certain type or number of cases. Improvement and refinement of that discovery can then be made. True science operates at the forefront of knowledge and the way forward is often unclear.
The accepted view is that the virus enters a latent state in the sensory ganglia, from which it periodically re-emerges. This may explain why stress, both mechanical and emotional, can trigger an outbreak. A 2014 finding was that viral activity within the ganglia continues even during latency.* Apparently, most external reactivations are inhibited by another factor or factors.
Much recent research has explored latency-associated transcripts (LATs). These are protein chains (microRNA) which have some, as yet poorly understood, associations with latency. LATs are found in huge numbers in the sensory ganglia: 40,000-100,000 per neuron. One of the more definite findings is that LATs inhibit apoptosis, the process by which cells routinely die. By inhibiting this normal process of cell death and renewal, that is, replacement with new, uninfected cells, latency is prolonged. The precise functions of LATs are still unknown.
* Ma JZ, Russell TA, Spelman T, Carbone FR, Tscharke DC (2014) Lytic Gene Expression is Frequent in HSV-1 Latent Infection and Correlates with the Engagement of a Cell-Intrinsic Transcriptional Response. PLoS Pathog 10(7): e1004237. doi:10.1371/journal.ppat.1004237
A lot of attention which has been given to potential HSV vaccines. People need to appreciate how vaccines and the immune system work.
Many, if not most, pathogens (disease-causing entities) succeed by proliferating wildly during the early stages of infection. Malaria is a good example. This is a protozoa, a single cell organism. A mosquito might inject just a few malaria cells into its victim's bloodstream, which then replicate at a great rate. By the time the victim's immune system has woken up to the new pathogen, it's too late. All the immune system can do then is try to contain it.
A vaccine works by readying the immune system so that it recognises the pathogen if and when infection occurs. If those handful of introduced malaria cells can be recognised and killed straightaway, disease is averted. Administering a vaccine after infection has become established will give, at best, only temporary or marginal results.
Vaccines fall into a broader class of substances called immunomodulators. These do not act directly against a pathogen but instead modify the immune response to it. Of course usually it is desired to boost the immune response. The problem is that the gain obtained is invariably short-lived and each successive boost will be less. L-Lysine appears to act chiefly as an immunomodulator.
This is not to say that vaccines and immunomodulators in general are useless, only that they give temporary benefit and must be administered at the right time.
Some aspects of latency have been neglected. There are suggestions in the Hopeful trials and elsewhere that certain treatments are capable of altering the course of infection. For instance, reducing the frequency of outbreaks is part-way to a cure. Reliably achieving this even for a minority of sufferers would be a significant breakthrough. However, proving such an effect requires convincing data taken from adequately large sample groups. Proving it seems to be as difficult as achieving it.