Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells.
The six group B coxsackieviruses (CVBs) are highly prevalent human pathogens that cause viremia followed by involvement of different organs. Clinical and experimental evidence suggests that CVBs can induce kidney injury, but the susceptibility of human renal cells to these viruses is unknown. By using pure cultures of human glomerular and tubular cells, we demonstrated that all CVBs are capable of productively infecting renal cells of three different histotypes. Distinct pathogenic effects were observed. Proximal tubular epithelial cells and, to a lesser extent, glomerular podocytes were highly susceptible to CVBs; in both cases, infection led to cytolysis. In contrast, glomerular mesangial cells supported the replication of the six CVBs but failed to develop overt cytopathologic changes. Mesangial cells continued to produce infectious progeny for numerous serial subcultures (i.e., more than 50 days), especially with type 1, 3, 4, and 5 viruses. In the above cells, persistent infection induced the de novo synthesis of platelet-derived growth factor A/B and enhanced the release of transforming growth factor beta1/2. These two factors are important mediators of progression from glomerular inflammation to glomerulosclerosis. CVB replication appeared also to impair the phagocytic and contractile activity of mesangial cells. Loss of these properties--which are important in glomerular physiopathology--may contribute to the development of progressive nephropathy. The results show that CVBs induce distinct effects in different types of cultured renal cells and suggest that CVB infections may be associated with both acute and progressive renal injury.
Conaldi
P G
PG
Department of Clinical and Biological Sciences, University of Pavia, Varese, Italy.
Biancone
L
L
Bottelli
A
A
De Martino
A
A
Camussi
G
G
Toniolo
A
A
D016207:Cytokines / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D029822:Enterovirus B, Human / Q000502:physiology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism / Q000821:virology; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism / Q000821:virology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D014407:Tumor Cells, Cultured; D017735:Virus Latency
D016207:Cytokines