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76 With respect to the cell receptor, the high molecular weight glycoprotein a-dystroglycan has been identi ed as a major receptor for Old World arenaviruses77 Dystroglycan is encoded as a glycoprotein precursor and posttranslationally processed to form the peripheral protein a-dystroglycan and the membrane-spanning protein b-dystroglycan, a complex highly expressed in a variety of cells and reported as a molecular link between the extracellular matrix and the actin-based cytoskeleton78 The situation with the New World arenaviruses is less clear: the assay of virus entry into mouse cells expressing or lacking a-dystroglycan together with a virus overlay protein blot assay demonstrated that only clade C viruses ( OLV and LATV) used a-dystroglycan as a major receptor79 By contrast, New World clade A and B arenaviruses appeared to use a different receptor or coreceptor for cell binding.

The framework uses descriptor objects to hold transfer request information, whether or not the controller supports scatter-gather. Controllers that do support scatter-gather need the descriptor information to be supplied in a format that is speci c to that particular hardware controller. This is shown as the SPlatDmaDesc structure on the diagram. If the controller doesn t support scatter-gather, then the framework uses a default descriptor structure, SDmaPseudoDes (not shown on the diagram). The pseudo descriptor contains the following information listed. Hardware-speci c descriptors generally contain similar information: 1. Transfer source location information. This can be either the address of a memory buffer or a 32-bit value identifying a particular peripheral. For memory addresses, this may hold either the linear or physical address of the buffer 2. Transfer destination location information (same format as 1)

Figure 15.19. Alive particles (hA ) for VTRPc at different time instances (n = 5000).

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A possible explanation to this behavior of VTRPC is the way the protocol modi es the transmission range by making small, constant steps. At the early stages of the network s operation, when only a small number of particles have died, these small steps suf ce to reach the sink. However, as the distance of the closest still-active

The protein nature of the cell receptor for JUNV, a clade B arenavirus, was demonstrated by enzymatic treatment, but the cellular protein was not identi ed80 The use of different receptors by viruses of the same family is not a surprising nding and may be related to biological differences in cell tropism or pathogenicity among viruses81 In fact, LCMV strains presenting point mutations in GP1 and differing in their pathogenic potential for mice also exhibited a differential binding af nity to a-dystroglycan: those strains with a high af nity of binding to a-dystroglycan invariably established a persistent infection in mice, whereas the mouse infection with LCMV variants with low level or no binding to a-dystroglycan was rapidly cleared.

3. 4.

350 300 Alive Particles 250 200 150 100 50 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 Distance from Sink (section)

The number of bytes to be transferred General information, such as whether the source/destination is a memory address or a peripheral identi er, whether memory addresses contain linear or physical addresses and whether these need to be post-incremented during transfer 32-bits of PSL-speci c information provided by the client.

82 These results are indicative of the association between receptor usage and pathogenesis and point out the need for the identi cation of the additional receptors or coreceptors utilized by arenaviruses, particularly those highly pathogenic members of the New World clade B associated to HF such as JUNV, MACV, SABV, and GTOV (see Table 51) The blockade of virus binding is very valuable as an antiviral therapeutic strategy because it allows us to establish a rst barrier to suppress infection For LCMV and LASV, two Old World arenaviruses that utilize a-dystroglycan as the cell receptor, it has been reported that the addition of the soluble a-dystroglycan blocked virus infection in vitro77 In another type of experimental approach,.

Figure 15.20. Alive particles (hA ) for VTRPm at different time instances (n = 5000).

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