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			PubMed Journals: J Virol

  Source:		PMID: 19297479
  Download:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681954/pdf/2272-08.pdf

    		J Virol. 2009 Jun;83(11):5451-65. doi:
     		10.1128/JVI.02272-08. Epub 2009 Mar 18.

			Differential virological and immunological
			outcome of severe acute respiratory syndrome
			coronavirus infection in susceptible and
			resistant transgenic mice expressing human
			angiotensin-converting enzyme 2.

			Yoshikawa N(1), Yoshikawa T, Hill T, Huang
			C, Watts DM, Makino S, Milligan G, Chan
			T, Peters CJ, Tseng CT.

			Author Information
			(1) Department of Microbiology and Immunology,
			University of Texas Medical Branch, Galveston,
			TX 77555-0609, USA.

			We previously reported that transgenic (Tg)
			mice expressing human angiotensin-converting enzyme 2
			(hACE2), the receptor for severe acute
			respiratory syndrome coronavirus (SARS-CoV), were
			highly susceptible to SARS-CoV infection,
			which resulted in the development of disease
			of various severity and even death in some
			lineages. In this study, we further characterized
			and compared the pathogeneses of SARS-CoV
			infection in two of the most stable Tg lineages,
			AC70 and AC22, representing those susceptible
			and resistant to the lethal SARS-CoV infection,
			respectively. The kinetics of virus replication
			and the inflammatory responses within the
			lungs and brains, as well as the clinical
			and pathological outcomes, were assessed
			in each lineage. In addition, we generated
			information on lymphocyte subsets and
			mitogen-mediated proliferation of splenocytes.
			We found that while both lineages were permissive
			to SARS-CoV infection, causing elevated
			secretion of many inflammatory mediators
			within the lungs and brains, viral infection
			appeared to be more intense in AC70 than
			in AC22 mice, especially in the brain. Moreover,
			such infection was accompanied by a more
			profound immune suppression in the former,
			as evidenced by the extensive loss of T
			cells, compromised responses to concanavalin
			A stimulation, and absence of inflammatory
			infiltrates within the brain. We also found
			that CD8(+) T cells were partially effective
			in attenuating the pathogenesis of SARS-CoV
			infection in lethality-resistant AC22 mice.
			Collectively, our data revealed a more intense
			viral infection and immunosuppression in
			AC70 mice than in AC22 mice, thereby providing
			us with an immunopathogenic basis for the
			fatal outcome of SARS-CoV infection in the
			AC70 mice.

			DOI: 10.1128/JVI.02272-08 PMCID: PMC2681954
			PMID: 19297479 [Indexed for MEDLINE]

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