tetano
Editor, Senior Moderator
DOI: 10.3201/eid1610.100108
Suggested citation for this article: Keynan Y, Juno J, Meyers A, Ball TB, Kumar A, Rubinstein
E, et al. Chemokine receptor 5 Δ32 allele in patients with severe pandemic (H1N1) 2009. Emerg
Infect Dis. 2010 Oct; [Epub ahead of print]
Chemokine Receptor 5 Δ32 Allele
in Patients with Severe
Pandemic (H1N1) 2009
Yoav Keynan, 1 Jennifer Juno, 1 Adrienne Meyers, T. Blake Ball, Anand Kumar,
Ethan Rubinstein, and Keith R. Fowke
Chemokine receptor 5 (CCR5) is a protein that belongs to the β-chemokine receptor family and is expressed primarily on T cells, macrophages, and dendritic cells. CCR5 plays a role in mediating leukocyte chemotaxis in response to its ligands, which include RANTES, MIP-1a, and MIP-1b. It may help direct many immune cell subsets, including regulatory T cells and
Th17 cells, to sites of infection. CCR5 is also 1 of 2 common co-receptors for HIV. Until recently, understanding the role of CCR5 in supporting the antiviral immune response was limited to appreciation of the role of receptor deficiency in protecting from HIV infection and disease progression. Persons who are homozygous for the CCR5Δ32 allele, a condition in which
a 32-bp deletion in the CCR5 gene prevents its expression on the cell surface, have been shown to have reduced susceptibility to HIV infection; the heterozygous state delays HIV disease progression (1–3). However, homozygosity of the Δ32 allele has recently been shown to be
associated with increased risk for symptomatic and fatal West Nile virus infection (4). This association was confirmed in a larger meta-analysis (5); CCR5 facilitated directed movement of lymphocytes during infection in a mouse model of West Nile virus infection (6). A case report of
an adverse reaction to the yellow fever virus vaccine in a person heterozygous for CCR5Δ32 and a link between the CCR5Δ32 allele and severe tickborne encephalitis symptoms suggest that
CCR5 may play a role in the immune response to other flavivirus infections as well (7,8).
Several reports have suggested a potential effect of the CCR5Δ32 allele on the response to influenza viruses. In mouse models, CCR5 is pivotal in directing CD8+ T cells to lung airways during challenge with Sendai virus (9); similarly, deaths among CCR5 –/– mice increase after
infection with influenza A virus (10). Because of the range of severity of recent pandemic (H1N1) 2009 infections and the possible role for CCR5 in the pulmonary immune response, we sought to determine whether patients requiring intensive care admission and respiratory support for severe pandemic (H1N1) 2009 were more likely to carry the CCR5Δ32 allele than were members of the general population.
full article
http://www.cdc.gov/eid/content/16/10/PDFs/10-0108.pdf
Suggested citation for this article: Keynan Y, Juno J, Meyers A, Ball TB, Kumar A, Rubinstein
E, et al. Chemokine receptor 5 Δ32 allele in patients with severe pandemic (H1N1) 2009. Emerg
Infect Dis. 2010 Oct; [Epub ahead of print]
Chemokine Receptor 5 Δ32 Allele
in Patients with Severe
Pandemic (H1N1) 2009
Yoav Keynan, 1 Jennifer Juno, 1 Adrienne Meyers, T. Blake Ball, Anand Kumar,
Ethan Rubinstein, and Keith R. Fowke
Chemokine receptor 5 (CCR5) is a protein that belongs to the β-chemokine receptor family and is expressed primarily on T cells, macrophages, and dendritic cells. CCR5 plays a role in mediating leukocyte chemotaxis in response to its ligands, which include RANTES, MIP-1a, and MIP-1b. It may help direct many immune cell subsets, including regulatory T cells and
Th17 cells, to sites of infection. CCR5 is also 1 of 2 common co-receptors for HIV. Until recently, understanding the role of CCR5 in supporting the antiviral immune response was limited to appreciation of the role of receptor deficiency in protecting from HIV infection and disease progression. Persons who are homozygous for the CCR5Δ32 allele, a condition in which
a 32-bp deletion in the CCR5 gene prevents its expression on the cell surface, have been shown to have reduced susceptibility to HIV infection; the heterozygous state delays HIV disease progression (1–3). However, homozygosity of the Δ32 allele has recently been shown to be
associated with increased risk for symptomatic and fatal West Nile virus infection (4). This association was confirmed in a larger meta-analysis (5); CCR5 facilitated directed movement of lymphocytes during infection in a mouse model of West Nile virus infection (6). A case report of
an adverse reaction to the yellow fever virus vaccine in a person heterozygous for CCR5Δ32 and a link between the CCR5Δ32 allele and severe tickborne encephalitis symptoms suggest that
CCR5 may play a role in the immune response to other flavivirus infections as well (7,8).
Several reports have suggested a potential effect of the CCR5Δ32 allele on the response to influenza viruses. In mouse models, CCR5 is pivotal in directing CD8+ T cells to lung airways during challenge with Sendai virus (9); similarly, deaths among CCR5 –/– mice increase after
infection with influenza A virus (10). Because of the range of severity of recent pandemic (H1N1) 2009 infections and the possible role for CCR5 in the pulmonary immune response, we sought to determine whether patients requiring intensive care admission and respiratory support for severe pandemic (H1N1) 2009 were more likely to carry the CCR5Δ32 allele than were members of the general population.
full article
http://www.cdc.gov/eid/content/16/10/PDFs/10-0108.pdf