PubMed Journals: J Virol

  Source:		PMID: 16282461
  Download:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1287568/pdf/1240-05.pdf

    		J Virol. 2005 Dec;79(23):14614-21.
			ACE2 receptor expression and
			severe acute respiratory syndrome
			coronavirus infection depend on
			differentiation of human airway

			Jia HP(1), Look DC, Shi L, Hickey M, Pewe
			L, Netland J, Farzan M, Wohlford-Lenane
			C, Perlman S, McCray PB Jr.

			Author Information
			(1) Department of Pediatrics, 240-G EMRB,
			Carver College of Medicine, University of Iowa,
			Iowa City, IA 52242, USA.

			Studies of patients with severe acute respiratory syndrome
			(SARS) demonstrate that the respiratory
			tract is a major site of SARS-coronavirus
			(CoV) infection and disease morbidity. We
			studied host-pathogen interactions using
			native lung tissue and a model of
			well-differentiated cultures of primary
			human airway epithelia. Angiotensin converting
			enzyme 2 (ACE2), the receptor for both the
			SARS-CoV and the related human respiratory
			coronavirus NL63, was expressed in human
			airway epithelia as well as lung parenchyma.
			As assessed by immunofluorescence staining
			and membrane biotinylation, ACE2 protein
			was more abundantly expressed on the apical
			than the basolateral surface of polarized
			airway epithelia. Interestingly, ACE2 expression
			positively correlated with the differentiation
			state of epithelia. Undifferentiated cells
			expressing little ACE2 were poorly infected
			with SARS-CoV, while well-differentiated
			cells expressing more ACE2 were readily
			infected. Expression of ACE2 in poorly
			differentiated epithelia facilitated SARS
			spike (S) protein-pseudotyped virus entry.
			Consistent with the expression pattern of
			ACE2, the entry of SARS-CoV or a lentivirus
			pseudotyped with SARS-CoV S protein in
			differentiated epithelia was more efficient
			when applied to the apical surface. Furthermore,
			SARS-CoV replicated in polarized epithelia
			and preferentially exited via the apical
			surface. The results indicate that infection
			of human airway epithelia by SARS coronavirus
			correlates with the state of cell differentiation
			and ACE2 expression and localization. These
			findings have implications for understanding
			disease pathogenesis associated with SARS-CoV
			and NL63 infections.

			DOI: 10.1128/JVI.79.23.14614-14621.2005
			PMCID: PMC1287568 PMID: 16282461 [Indexed
			for MEDLINE]

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