Clinical variability, host immunity
The clinical features and outcomes seen with viral disease vary greatly among patients with the same microbe, and what causes this is the most important unresolved question in the infectious disease arena. Investigators point to various factors, such as the viral strain, latency site, or host immunity. Dr. Margolis favors the latter.
He discussed the epidemiology of herpes simplex virus (HSV)-1 ARN, a rare disease that occurs in 1 or 2 people per 5 million annually, despite that 80% of individuals have HSV in them. HSV-1 ARN is not an isolated entity. Affected patients also have a high incidence of a second eye disease and central nervous system involvement in addition to chronic iritis and late relapses.
“These patients are prone to central HSV infection but not peripheral (skin) disease,” he noted.
In a look-back investigation, Dr. Margolis and his colleagues found that of 7 patients with ARN, all also had encephalitis, which raises the question about a genetic component.
When considering immune risk factors for HSV, age and atopy are risks for ocular HSV; the C21orf91 genotype is a risk factor for labial HSV, and the TLR2 polymorphisms are risks for HSV encephalitis.
“Are these same polymorphisms in these genes responsible for patients who develop HSV-1 ARN?” he asked. This is not isolated to HSV-1 ARN but is apparent in other infectious diseases.
“We now understand that highly specific allelic polymorphisms predispose a limited number of individuals to diseases caused by viruses that otherwise only rarely cause overt disease,” he said. “A virus present in all of us may cause disease only in those unfortunate enough to have a specific genetic make-up.”
He added that research is showing a number of single gene variants can convey susceptibility or resistance to various pathogens.