DESCRIPTION


In the past, viral proteins that are secreted from the infected cell and bind with high affinity chemokines and inhibit their pro-inflammatory activity have been identified. In recent investigations we have identified the first viral protein (glycoprotein G, gG) that binds chemokines and, in contrast to other chemokine binding proteins, potentiates the ability of chemokines to induce cell migration. Chemokines are important mediators of the inflammatory response that induce migration of immune cells into tissues. Protein gG is encoded by herpes simplex virus 1 and 2 (HSV-1 and -2), important human pathogens that cause frequent clinical problems. In addition, the ability of gG to potentiate chemokine activity has important therapeutic applications in human diseases characterized by defects in immune cell migration.

The invention offers two therapeutic applications:

1. Treatment of HSV-1- and HSV-2-associated diseases.

Among the diseases associated with HSV-1 and HSV-2 infections are meningitis, encephalitis, corneal keratitis and blindness. HSV infections cause a high economical impact in companies.
In addition, HSV represents a risk for neonates because the infection during the third term of gestation and/or delivery may lead to disseminating disease, multiple organ failure, including the central nervous system (CNS), and death of the fetus or neonate. In the absence of anti-viral therapy, mortality reaches 80% in the disseminating disease and 50% in those patients with symptoms in the CNS. Most of the infected neonates will develop neurological problems. In addition, the modulation of chemokine activity is associated with the presence of cellular infiltrate characteristic of the acute phase of HSV infection, an infiltrate that plays a role in the pathogenesis of HSV. Therefore, the blockade of gG activity in the context of HSV infection has a great therapeutic potential to limit viral replication and the pathology caused by the virus.

2. Treatment of human diseases characterized by alterations in the migration of immune cells.

The ability of gG to potentiate cell migration may be used to compensate for the limited cell migration found in a number of human diseases such as: cardiac ischemia, stem cell post-infarct therapy, acute coronary syndrome, spontaneous bronchoalveolar cell, Q fever.

INNOVATIVE ASPECTS


Until now, viral proteins that bind chemokines, important mediators of inflammation, have been found in viruses with no clinical relevance. The protein gG from HSV is the first viral protein that binds chemokines and potentiates the biological activity of chemokines, having therapeutic applications in human diseases characterized by alterations in the migration of immune cells. In addition, the inhibition of the activity of gG may restrict HSV infection/replication and the pathogenesis caused by these important human pathogens.

COMPETITIVE ADVANTAGES


It supposes the treatment of HSV-1- and HSV-2-associated diseases like meningitis, encephalitis, corneal keratitis and blindness and treatment of diseases characterized by alterations in the migration of immune cells like cardiac ischemia, stem cell post-infarct therapy, acute coronary syndrome, spontaneous bronchoalveolar cell or Q fever.

KEYWORDS


006001019 Virus, virology/antibiotics/ bacteriology
006001016 Pharmaceutical products/ medicine

PATENT


PCT/ ES07/070139 applied for 2007-07-20

CONTACT


Eva Gabaldón
email: eva.gabaldon@orgc.csic.es
phone: +34 91 585 46 23


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