Trusted Resources: Evidence & Education
Scientific literature and patient education texts
Restriction of HIV-1 infection in sickle cell disease trait
source: American Society of Hematology
year: 2017
authors: Namita Kumari, Javed Khan, Tatiana Ammosova, Asrar Ahmad, Sharmin Diaz, Sohail Rana, Sergei Nekhai
summary/abstract:We recently showed that in Sickle Cell Disease (SCD), activation of anti-viral restriction factor SAMHD1 and NF-κB inhibitor, IkBα prevented ex vivo HIV-1 infection. SAMHD1 activation was due to its reduced phosphorylation by CDK2, whose activity was inhibited by reduced intracellular iron levels in SCD peripheral blood mononuclear cells (PBMC). We also found that a hazard ratio associated with HIV infection among 11,412 SCD trait subjects was 1.0% comparing to >2% HIV-1 infection among African-Americans in USA. We compared 9 HbAS HIV-1 infected individuals with 107 HbAA or HbAC HIV-1 infected individuals who were enrolled at Howard University clinic. While hemoglobin levels in these two groups were not significantly different, HIV-1 viral load was significantly lower in HbAS group as well the number of HIV-1 associated complications (Hospitalization) were reduced. In the present study, we analyzed ex vivo HIV-1 infection of SCD trait PBMC and determined the expression of iron and hypoxia-regulated host factors including HO-1, NFκB, IKK, IKBα that are implicated in HIV-1 replication. We also analyzed CDK2 activity, SAMHD1 phosphorylation and RNR2 expression in SCD trait PBMCs. One round HIV-1 infection was significantly reduced in in SCD trait PBMC. Expression of HO-1 and IKBα was upregulated in SCD trait whereas IKK and NF-κB expression was downregulated. While CDK2 activity and SAMHD1 phosphorylation were not changed, RNR2 expression was reduced. Expression levels of HIV-1 env and gag mRNA were significantly lower in HIV-1 infected SCD trait subjects. In the same patients, HO-1 and IKBα mRNA levels were upregulated comparing to HIV-1+ HbAA or HbAC subjects. Our findings suggest that HIV-1 infection might be deregulation in SCD trait and that iron metabolism and hypoxia might play a role in this deregulation.
organization: Howard University, Washington, DCread more
Related Content
-
SCDAA News Advisory: SCDAA Statement on Exa-cel Gene TherapyOn October 31, 2023, the Food and Drug A...
-
Higher Executive Abilities Following a Blood Transfusion in Children and Young Adults With Sickle Cell DiseaseIndividuals with sickle cell disease (SC...
-
Crizanlizumab 5.0 mg/kg increased the time to first on-treatment sickle cell pain crisis (SCPC) and the likelihood o...Background: In the 52-week SUSTAIN stud...
-
Ex-rutgers stars Devin and Jason McCourty top $1M in fundraising for charityAbout 200 donors showed up Saturday afte...
-
Children’s Hospital of WisconsinThe Sickle Cell Research Program at Chil...
-
IASCNAPA Sickle Cell Disease Conference: Treating the Whole PersonDate: April 14-15, 2021 Place: Online/V...
-
Sickle Cell, Racism, and the Armor of Radical Self Lovehttps://www.youtube.com/watch?v=m45DuiSc...
To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences. More Information
The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.