Abstract
Human cytomegalovirus (HCMV) completes its final envelopment on intracellular membranes before it is released from the cell. The mechanisms underlying these processes are not understood. Here we studied the role of Rab27a, a regulator of lysosome-related organelle transport, in HCMV production. HCMV infection increased Rab27a expression, and recruitment of Rab27a to membranous strutures at the assembly site. Immuno-gold labelling demonstrated association of Rab27a with viral envelopes. CMV production was reduced after knock-down of Rab27a, and in Rab27a-deficient ashen melanocytes. This study shows a requirement for Rab27a in the CMV life cycle and suggests that CMV and LRO biogenesis share common molecular mechanisms.
Highlights
Human cytomegalovirus (HCMV), a member of the Betaherpesvirinae subfamily, is a widespread pathogen in man that causes an asymptomatic and often times latent infection
While the nature of the membrane that HCMV uses for its envelope has been controversial for some time [3,4,5,6,7,8,9], our recent results show that final envelopment occurs into a hybrid compartment or in transport vesicles between the trans-Golgi network (TGN) and endosomes [10], the mechanism of which remains to be defined
In HCMV-infected cells the scattered distribution of Rab27a was changed and Rab27a appeared to be recruited to the assembly site where it partially co-localised with HCMV glycoprotein H (Fig. 1B)
Summary
Human cytomegalovirus (HCMV), a member of the Betaherpesvirinae subfamily, is a widespread pathogen in man that causes an asymptomatic and often times latent infection. HCMV consists of a capsid containing the double-stranded DNA genome surrounded by the tegument and a lipid envelope with embedded glycoproteins. Capsids acquire a set of tegument proteins and undergo a final envelopment by wrapping into membranes before they are secreted to the extra-cellular space [2]. While the nature of the membrane that HCMV uses for its envelope has been controversial for some time [3,4,5,6,7,8,9], our recent results show that final envelopment occurs into a hybrid compartment or in transport vesicles between the trans-Golgi network (TGN) and endosomes [10], the mechanism of which remains to be defined
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