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In the central nervous system, connective tissue, and skeletal and cardiac muscle, capillary endothelial cells are supported by a dense basement membrane, which raises an additional barrier to viral passage into the tissue (Fig. 2.18 and 2.20). In the central nervous system, the basement membrane, formed in part by astrocytic extensions (called “endfeet”) that align with the basolateral surface of the capillary endothelium, is the foundation of the blood-brain barrier (Fig. 2.21).

Not all capillaries in tissues adhere to one of these three types: for example, in several well-defined parts of the brain, the capillary epithelium is loosely joined together, and the basement membrane is sparse, affording an easier passage for some neurotropic viruses . These highly vascularized sites include the choroid plexus, a sheet of tissue that lies within the brain ventricles and that produces more than 70% of the cerebrospinal fluid that bathes the spinal cord and affords protective cushioning. Some viruses (mumps virus and certain togaviruses) pass through the capillary endothelium and enter the stroma of the choroid plexus, where they may then cross the epithelium into the cerebrospinal fluid either by transcytosis or by directed release following production of progeny virus particles. Once in the cerebrospinal fluid, infection can spread to the ependymal cells lining the ventricles and the underlying brain tissue (Fig. 2.21). Other viruses (picornaviruses) may infect directly, or be transported across the capillary endothelium. Some viruses (human immunodeficiency virus type 1 and measles virus) cross the endothelium within infected monocytes or lymphocytes (the Trojan Horse approach, described earlier). Increased local permeability of the capillary endothelium, caused, for example, by certain hormones, may also facilitate virus entry into the brain and spinal cord.

Figure 2.20 How viruses travel from blood to tissues with basement membranes. Schematic of a capillary (similar to Fig. 2.19, right), illustrating different pathways by which viruses may leave the blood and enter underlying tissues. Adapted from Nathanson N (ed). 2007. Viral Pathogenesis and Immunity (Academic Press, London, United Kingdom), with permission.