The human cytomegalovirus ul11 protein interacts with the receptor tyrosine phosphatase cd45, resulting in functional paralysis of t cells

Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV

Lashed by sharks, pelted by demons, drowned for apostasy: the value of myths that explain geohazards in the Asia-Pacific region

The critical analysis of myths (traditional oral tales) can lead to an improved understanding of geohazards. This paper examines three groups of myths (volcano, earthquake, and coastal change) from Asia-Pacific cultures and shows how their analysis might contribute to the identification of unrealized geohazards in particular places as well as the magnitudes and recurrence intervals of these hazards. Many volcano myths involve gods within the mountains who are periodically angered and punish the people living nearby; through gifts, volcano gods are appeased, a process that has been widespread in parts of the Asia-Pacific region. Other volcano myths allow people to recognize eruption precursors or identify eruption locations. Earthquake myths often involve an animal within the Earth failing to support it upright. More recently, earthquakes have been interpreted as an expression of divine anger at the state of (local) human affairs. Myths also refer to earthquake precursors and have proved effective in eliciting appropriate community responses following tsunamigenic earthquakes. Coastal-change myths are more likely to be memories of long-term (postglacial) coastal change on which extreme-wave events were superimposed. The latter are the most memorable details in myths but the consequences of these events can be explained only by long-term change. Abrupt changes to Asia-Pacific coasts have also been captured by myths, ranging from local collapses of cliffed coasts to the disappearance of entire islands in the Pacific Ocean. Myths can supply information around the nexus of geological and historical data sources, particularly between 102 and 104 years ago. As such, myths have the potential to contribute “missing” data to long-term geohazard chronologies and thereby improve hazard understanding and preparedness. Myths from Asia-Pacific cultures that refer to community responses to geohazards can also be useful in contemporary strategies for awareness-raising. Geographers are uniquely qualified to identify and interpret myths that refer to geohazards. There is potential for many more such myths to be gathered from the Asia-Pacific region