Immune-Mediated Control of a Dormant Neurotropic RNA Virus Infection.

Genomic material from many neurotropic RNA viruses (e.g., measles virus [MV], West Nile virus [WNV], Sindbis virus [SV], rabies virus [RV], and influenza A virus [IAV]) remains detectable in the mouse brain parenchyma long after resolution of the acute infection.

Know Your Body Through Intrinsic Goals.

The first "object" that newborn children play with is their own body. This activity allows them to autonomously form a sensorimotor map of their own body and a repertoire of actions supporting future cognitive and motor development. Here we propose the theoretical hypothesis, operationalized as a computational model, that this acquisition of body knowledge is not guided by random motor-babbling, but rather by autonomously generated goals formed on the basis of intrinsic motivations.

CD4 T cells require either B cells or CD8 T cells to control spread and pathogenesis of a neurotropic infection.

Immunity within the brain, specifically to virus-infected neurons, must be controlled to prevent neuron loss and impairment, though the process by which this occurs remains unclear. Here, we use a mouse model of neuron-restricted measles virus infection, in which immunocompetent adults survive challenge, whereas T and B cell-deficient mice succumb. This model allowed us to more precisely define the contributions of CD4 T cells, CD8 T cells, and B cells in neuroprotection.

Humour production may enhance observational learning of a new tool-use action in 18-month-old infants.

Many studies have shown that making children laugh enhances certain cognitive capacities such as attention, motivation, perception and/or memory, which in turn enhance learning. However, no study thus far has investigated whether laughing has an effect on learning earlier in infancy. The goal of this study was to see whether using humour with young infants in a demonstration of a complex tool-use task can enhance their learning.

CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

Although viruses have been implicated in central nervous system (CNS) diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage.

Identification of interaction domains within the UL37 tegument protein of herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1) UL37 is a 1123 amino acid tegument protein that self-associates and binds to the tegument protein UL36 (VP1/2). Studies were undertaken to identify regions of UL37 involved in these protein-protein interactions. Coimmunoprecipitation assays showed that residues within the carboxy-terminal half of UL37, amino acids 568-1123, are important for interaction with UL36.

Virion incorporation of the herpes simplex virus type 1 tegument protein VP22 is facilitated by trans-Golgi network localization and is independent of interaction with glycoprotein E.

HSV-1 virions contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The molecular mechanisms that facilitate incorporation of tegument proteins are poorly characterized. The tegument protein VP22 interacts with VP16 and the cytoplasmic tail of glycoprotein E (gE).

Lymphocytic choriomeningitis virus-induced mortality in mice is triggered by edema and brain herniation.

Although much is known about lymphocytic choriomeningitis virus (LCMV) infection and the subsequent immune response in its natural murine host, some crucial aspects of LCMV-mediated pathogenesis remain undefined, including the underlying basis of the characteristic central nervous system disease that occurs following intracerebral (i.c.) challenge.

The HSV-1 tegument protein pUL46 associates with cellular membranes and viral capsids.

The molecular mechanisms responsible for the addition of tegument proteins into nascent herpesvirus particles are poorly understood. To better understand the tegumentation process of herpes simplex virus type 1 (HSV-1) virions, we initiated studies that showed the tegument protein pUL46 (VP11/12) has a similar cellular localization to the membrane-associated tegument protein VP22. Using membrane flotation analysis we found that pUL46 associates with membranes in both the presence and absence of other HSV-1 proteins.

Incorporation of the herpes simplex virus type 1 tegument protein VP22 into the virus particle is independent of interaction with VP16.

Herpes simplex virus type 1 (HSV-1) virions contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The mechanisms underlying tegumentation remain largely undefined for all herpesviruses. Using glutathione S-transferase (GST) pulldowns and coimmunoprecipitation studies, we have identified a domain of the tegument protein VP22 that facilitates interaction with VP16.

Herpes simplex virus type 1 tegument proteins VP1/2 and UL37 are associated with intranuclear capsids.

The assembly of the tegument of herpes simplex virus type 1 (HSV-1) is a complex process that involves a number of events at various sites within virus-infected cells. Our studies focused on determining whether tegument proteins, VP1/2 and UL37, are added to capsids located within the nucleus. Capsids were isolated from the nuclear fraction of HSV-1-infected cells and purified by rate-zonal centrifugation to separate B capsids (containing the scaffold proteins and no viral DNA) and C capsids (containing DNA and no scaffold proteins).

A conserved region of the herpes simplex virus type 1 tegument protein VP22 facilitates interaction with the cytoplasmic tail of glycoprotein E (gE).

Herpes simplex virus type 1 (HSV-1) virions, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. Current evidence suggests that viral glycoprotein tails play a role in the recruitment of tegument-coated capsids to the site of final envelopment; vesicles derived from the trans-Golgi network. We have identified an interaction between VP22, an abundant tegument protein and the cytoplasmic tail of glycoprotein E (gE).