Many enveloped and non-enveloped animal viruses delay the penetration into the cytosol of host cells until they have arrived to endocytic vacuoles deep in the cytoplasm. The late timing is generally determined by a low pH-threshold for the acid-activated penetration process (pH 6.2-4.9), but there can be a combination of other reasons for a delay. Since late-penetrating viruses (L-PVs) must be sorted into the degradative pathway, they are particularly sensitive to perturbations that interfere with molecular sorting and proper maturation of endosomes, including switching of Rabs, formation of intraluminal vesicles, and microtubule-mediated transport. In this short review, we focus on L-PVs from several virus families, and their interactions with the endocytic machinery.
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