You are not logged in.
Openly accessible

HIV-1 Mutation and Recombination Rates Are Different in Macrophages and T-cells

Cromer, Deborah, Schlub, Timothy E., Smyth, Redmond P., Grimm, Andrew J., Chopra, Abha, Mallal, Simon, Davenport, Miles P. and Mak, Johnson 2016, HIV-1 Mutation and Recombination Rates Are Different in Macrophages and T-cells, Viruses, vol. 8, no. 4, pp. 1-14, doi: 10.3390/v8040118.

Attached Files
Name Description MIMEType Size Downloads
mak-hiv1mutation-2016.pdf Published version application/pdf 3.00MB 5

Title HIV-1 Mutation and Recombination Rates Are Different in Macrophages and T-cells
Author(s) Cromer, Deborah
Schlub, Timothy E.
Smyth, Redmond P.
Grimm, Andrew J.
Chopra, Abha
Mallal, Simon
Davenport, Miles P.
Mak, JohnsonORCID iD for Mak, Johnson orcid.org/0000-0002-5229-5707
Journal name Viruses
Volume number 8
Issue number 4
Start page 1
End page 14
Total pages 14
Publisher MDPI
Place of publication Basel, Switzerland
Publication date 2016
ISSN 1999-4915
Keyword(s) HIV
evolution
mutation
recombination
Summary High rates of mutation and recombination help human immunodeficiency virus (HIV) to evade the immune system and develop resistance to antiretroviral therapy. Macrophages and T-cells are the natural target cells of HIV-1 infection. A consensus has not been reached as to whether HIV replication results in differential recombination between primary T-cells and macrophages. Here, we used HIV with silent mutation markers along with next generation sequencing to compare the mutation and the recombination rates of HIV directly in T lymphocytes and macrophages. We observed a more than four-fold higher recombination rate of HIV in macrophages compared to T-cells (p < 0.001) and demonstrated that this difference is not due to different reliance on C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 5 (CCR5) co-receptors between T-cells and macrophages. We also found that the pattern of recombination across the HIV genome (hot and cold spots) remains constant between T-cells and macrophages despite a three-fold increase in the overall recombination rate. This indicates that the difference in rates is a general feature of HIV DNA synthesis during macrophage infection. In contrast to HIV recombination, we found that T-cells have a 30% higher mutation rate than macrophages (p < 0.001) and that the mutational profile is similar between these cell types. Unexpectedly, we found no association between mutation and recombination in macrophages, in contrast to T-cells. Our data highlights some of the fundamental difference of HIV recombination and mutation amongst these two major target cells of infection. Understanding these differences will provide invaluable insights toward HIV evolution and how the virus evades immune surveillance and anti-retroviral therapeutics.
Language eng
DOI 10.3390/v8040118
Field of Research 110804 Medical Virology
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Grant ID NHMRC 1025270
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30083326

Document type: Journal Article
Collections: School of Medicine
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in TR Web of Science
Scopus Citation Count Cited 0 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 75 Abstract Views, 6 File Downloads  -  Detailed Statistics
Created: Mon, 27 Jun 2016, 12:58:12 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.