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Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.

The release of extracellular vesicles, whether MVs (microvesicles) or exosomes, from host cells or intracellular pathogens is likely to play a significant role in the infection process. Host MVs may fuse with pathogen surfaces to deliver host complement regulatory proteins. They may also deliver cytokines that enhance invasion. Decoy functions are also possible. Whereas host MVs may direct pathogens away from their target cells, pathogen MVs may in turn redirect complement membrane-attack complexes away from their target pathogen. An understanding of the mechanisms of this interplay, bringing about both immune evasion and enhanced invasion, will help to direct future research with a view to rendering pathogens more susceptible to immune attack or in improving drug efficacy. It should also be possible to use MVs or exosomes isolated directly from the pathogens, or from the cells infected with pathogens, to provide alternative vaccination strategies.

Coxsackievirus B1, a member of the Picornaviridae family is a non-enveloped single-stranded RNA virus associated with human diseases including myocarditis and pancreatitis. Infection of the intestinal mucosa, lined by polarized epithelial cells, requires interaction of coxsackievirus with apically located DAF (decay-accelerating factor) before transport to the basolaterally located CAR (coxsackie and adenovirus receptor), where entry is mediated by endocytosis. As with many other non-enveloped viruses, coxsackievirus has to induce lysis of host cells in order to perpetuate infection. However, recent evidence indicates that virus spread to secondary sites is not only achieved by a lytic mechanism and a non-lytic cell–cell strategy has been suggested for coxsackievirus B3. A physical interaction between infected and non-infected cells has been shown to be an efficient mechanism for retroviral transmission and one type of extracellular vesicle, the exosome, has been implicated in HIV-1 transmission. HIV-1 also takes advantage of depolymerization of actin for spread between T-cells. Calpain-mediated depolymerization of the actin cytoskeleton, as a result of increases in intracellular calcium concentration during coxsackievirus infection, would result in a release of host cell-derived microvesicles. If so, we speculate that maybe such microvesicles, increasingly recognized as major vehicles mediating intercellular communication, could play a role in the intercellular transmission of non-enveloped viruses.

The important roles of extracellular vesicles in the pathogenesis of various diseases are rapidly being elucidated. As important vehicles of intercellular communication, extracellular vesicles, which comprise microvesicles and exosomes, are revealing important roles in cancer tumorigenesis and metastases and in the spread of infectious disease. The September 2012 Focused Meeting ‘Microvesiculation and Disease’ brought together researchers working on extracellular vesicles. The papers in this issue of Biochemical Society Transactions review work in areas including HIV infection, kidney disease, hypoxia-mediated tumorigenesis and down-regulation of immune cell functions in acute myeloid leukaemia by tumour-derived exosomes. In all cases, microvesicles and exosomes have been demonstrated to be important factors leading to the pathophysiology of disease or indeed as therapeutic vehicles in possible new treatments. The aim was, having enhanced our molecular understanding of the contribution of microvesicles and exosomes to disease in vitro, to begin to apply this knowledge to in vivo models of disease.