Dr. Pablo González
Young Investigator
Universidad Católica de Chile
Every day we are exposed to viruses That Can Affect our health seriously. Due to the diversity and Characteristics of the virus, These microbes are difficult to treat and Often must be controlled by the immune system, Extending the recovery time. While chronically large number of viruses to infect host acutely (transient infection), some viruses infect host persisting in the single for the rest of his life.
The main interest of my research laboratory is to identify, characterize and counteract the action of molecules that allow some viruses to infect host of chronic manner. We are particularly interested in the study of the herpes virus family, especially those affecting the mucous membranes, such as herpes simplex virus-2 (HSV-2). The virus persists in the host in a dormant state characterized by symptomatic reactivations asymptomatic (skin lesions) or (no injury) to produce pathology and promote its diffusion. Currently, HSV-2 infects about 500 million people worldwide and there is no vaccine to prevent infection.
The main lines of research in my laboratory are:
A. Identification and characterization of virulence factors from HSV-2 involved in modulating the innate antiviral response and alter specific antiviral response. We are especially interested in the study of the surface glycoproteins of HSV-2 in these processes. To date, 11 have been described for surface glycoproteins of HSV-2.
B. Genetic manipulation of HSV-2 (recombinant strains) in order to express molecular factors that promote antiviral response in the host.
Viruses belonging to the Herpesviridae family, such as herpes simplex (HSV-1, HSV-2), varicella zoster virus (VZV, HHV-3), Epstein Bar virus (EBV, HHV-4), cytomegalovirus (CMV, HHV-5 ) and Kaposi sarcoma virus (KSV, HHV-8) have the ability to infect the host chronically, remaining in a state of latency which can result in sporadic reactivations and disease. The ability of these viruses to co-exist with the host involves the evolution of mechanisms for evasion of the immune response by these microbes and the development of skills that allow them to persist chronically in the individual.
The herpes simplex virus (HSV-1 and HSV-2) infects a large percentage of the population and its impact has been particularly increased in recent decades in developed countries. In the U.S., the prevalence of the virus in the population is estimated at 60% for HSV-1 and 20% for HSV-2. In parts of Africa the HSV-2 prevalence reaches up to 70%. After an episode of primary infection, HSV latently protects neuronal cells in the host to be able to reactivated later exposure to ultraviolet light and low as a result of immunosuppression immunity, aging and stress, among others. Currently, HSV is the leading cause of blindness due to infection and can cause encephalitis with high mortality in neonates. However, the most common clinical symptoms are caused by HSV mucosal ulcers. Surprisingly, most HSV-2 recurrences are usually asymptomatic, promoting the silent spread of the virus in the population. Furthermore, recently, it has been shown that HSV-2 increases four times the risk of contracting HIV, suggesting that HSV could modulate host susceptibility to other infections.
The herpes simplex virus genomes have approximately 150,000 bp large (> 80 genes) that encode a large number of virulence factors to evade the antiviral response of the host. These viral determinants allow the virus to evade the immune system function, including counteracting the action of complement, and the effectiveness of antibodies interfering with T cell recognition
While treatment with Acyclovir (nucleotide analogue) reduces disease caused by HSV-2 and HIV transmission from infected individuals to healthy individuals, this drug does not eradicate the virus completely host. It is therefore important to develop strategies to prevent infection with this virus, or promote the efficient elimination of the pathogen once infection has occurred. Recently, clinical stages aimed at developing vaccines against HSV-2, based on protein subunits (Chiron, GlaxoSmithKline), unsatisfactory results obtained in Phase 3 clinical studies. Though these formulations generated the development of neutralizing antibodies against the virus in vaccinated individuals the effectiveness of the vaccine did not exceed 20% protection. These disappointing results show the complexity of HSV infection and the need to develop new ways to combat it. Therefore, we are also interested in exploring new strategies for the prevention of infection caused by HSV-2.
Si bien el tratamiento con Acyclovir (análogo nucleótido) reduce la patología producida por HSV-2, así como la transmisión del virus desde individuos afectados hacia individuos sanos, este fármaco no erradica por completo el virus del hospedero. Por ello, es importante desarrollar estrategias que prevengan la infección con este virus, o bien promuevan la eliminación eficiente del patógeno una vez que la infección ya ha ocurrido. Recientemente, fases clínicas orientadas al desarrollo de vacunas contra HSV-2, basadas en subunidades proteicas (Chiron, GlaxoSmithKline), obtuvieron resultados insatisfactorios en estudios clínicos fase 3. Si bien estas formulaciones generaron el desarrollo de anticuerpos neutralizantes contra el virus en los individuos vacunados, la efectividad de la vacuna no superó el 20% de protección. Estos resultados desalentadores evidencian la complejidad de la infección por HSV, así como la necesidad de desarrollar nuevas alternativas para combatirlo. Por ello, estamos interesados también en explorar nuevas estrategias orientadas a la prevención de la infección producida por HSV-2.