The main interest of my research laboratory is to identify, characterize, and counteract the action of molecules that allow some viruses to persistently infect the host. We are particularly interested in studying viruses of the herpes family, primarily those that affect the skin, mucous membranes, and brain, such as herpes simplex viruses type 1 and 2 (HSV-1 and HSV-2). These viruses persist in the host in a latent state, characterized by symptomatic (skin lesions, ocular damage, encephalitis) or asymptomatic (without lesions, occurring in most people) reactivations. Importantly, both types of infections are associated with their spread. Currently, HSV-1 affects two-thirds of the world’s population and HSV-2 affects 10%, there are no vaccines to prevent infection by these viruses, and available therapies can be ineffective for some symptoms, such as skin infections.

The central lines of research:

1. Identification and characterization of host factors involved in viral replication, modulation of the cellular antiviral response, and modulation of the innate and adaptive antiviral response.
   
   
2. Identification and characterization of new antiviral compounds against herpes viruses from natural extracts or repurposing of drugs.
   
   
3. Determination of the role of cellular metabolic processes in the replicative cycles of HSV-1 and HSV-2, and in inflammatory processes.
   
   
4. Study of the effect of asymptomatic and latent HSV infection in the central nervous system on senescence and its susceptibility to disease and severity of inflammatory and autoimmune pathologies.
   
   

Viruses belonging to the Herpesviridae family, such as herpes simplex types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV, HHV-3), Epstein-Barr virus (EBV, HHV-4), cytomegalovirus (CMV, HHV-5), and Kaposi’s sarcoma-associated herpesvirus (KSHV, HHV-8), have the ability to persistently infect the host, maintaining a latent state that can result in sporadic reactivations and disease. The ability of these viruses to coexist with the host implies the evolution of mechanisms to evade the immune response and develop capabilities that allow them to persistently remain in the individual.

Herpes simplex viruses (HSV-1 and HSV-2) infect a large percentage of the population, and their incidence has particularly increased in recent decades in developed countries. In the US, the prevalence of these viruses in the population is estimated at 60% for HSV-1 and 20% for HSV-2. In some regions of Africa, HSV-2 reaches prevalences of up to 70%. After a primary infection episode, HSV remains latent in neuronal cells of the host to reactivate later under conditions of immunodepression, immunosuppression, and stimuli such as overexposure to high-energy light (ultraviolet), among others. Currently, HSV is the leading cause of infectious blindness and can produce encephalitis with sequelae in adults and high mortality in newborns. However, the most common clinical symptoms produced by HSV are ulcers on mucous membranes and skin. Surprisingly, most HSV recurrences are asymptomatic, promoting the silent spread of the virus in the population.

Herpes simplex viruses have large genomes of about 150,000 bp (>80 genes) that encode numerous virulence factors to evade the host’s antiviral response. These viral determinants allow the virus to escape the immune system’s function, counteracting, among other things, the action of the complement system, antigen presentation by professional antigen-presenting cells, the effectiveness of antibodies, and interfering with the activation and recognition of infected cells by T cells.

While treatment with acyclovir (a nucleoside analogue) reduces the pathology caused by HSV and the probability of death caused by these viruses, as well as the transmission of these viruses from affected individuals to healthy individuals, this drug and similar ones do not completely eradicate the virus from the host. Furthermore, they are not entirely effective in treating some clinical manifestations produced by HSV, such as skin lesions. Therefore, it is important to develop strategies to prevent infection with this virus or promote the efficient elimination of the pathogen once infection has occurred.

It is worth noting that phase 3 clinical trials developed almost a decade ago aimed at developing vaccines against HSV based on protein subunits and adjuvants obtained unsatisfactory results. Although these formulations promoted the development of neutralizing antibodies against the virus (in vitro) in vaccinated individuals, the effectiveness of the vaccine was not significant. These discouraging results highlight the complexity of HSV infection and the need to develop new alternatives to prevent it. Therefore, we are also interested in exploring new strategies aimed at preventing HSV infection.