A viral pathogen requires a specific cell surface sialic acid linkage and a host protease for activation. How do these requirements influence tissue tropism and the pathogen's portal-of-entry constraints?

• A. If the protease requirement is unmet, the virus will immediately convert into a bacterial form that can then attach to a wide range of tissues, negating any receptor-based tropism.
• B. Tropism is determined solely by the immune system; surface receptors and proteases are irrelevant because any tissue that is immunosuppressed will permit colonization regardless of receptor presence.
• C. The virus will be equally likely to colonize any tissue because sialic acid linkages and proteases are ubiquitous and uniform across all host surfaces, making portal of entry irrelevant for tissue specificity.
• D. Tropism is restricted to tissues that both present the correct sialic acid linkage and express the activating protease; therefore only portals of entry that deliver virus particles to those tissues (for example, nasal epithelium if both factors are present there) will support successful colonization.

Answer: (D)