Infection of the CD45RA+ (Naive) Subset of Peripheral CD8+ Lymphocytes by Human Immunodeficiency Virus Type 1 In Vivo

doi:10.1128/JVI.75.9.4091-4102.2001

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Journal of Virology, May 2001, p. 4091-4102, Vol. 75, No. 9
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4091-4102.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Infection of the CD45RA⁺ (Naive) Subset of Peripheral CD8⁺ Lymphocytes by Human Immunodeficiency Virus Type 1 In Vivo

S. McBreen,¹ S. Imlach,¹ T. Shirafuji,¹ G. R. Scott,² C. Leen,³ J. E. Bell,⁴ and P. Simmonds¹^,^*

Laboratory for Clinical and Molecular Virology, University of Edinburgh, Edinburgh EH9 1QH,¹ Department of Genitourinary Medicine, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW,² and Regional Infectious Diseases Unit³ and Department of Neuropathology,⁴ Western General Hospital, Edinburgh EH4 2XU, United Kingdom

Received 18 September 2000/Accepted 24 January 2001

To investigate the mechanism and functional significance of infection of CD8⁺ lymphocytes by human immunodeficiency virus type 1 (HIV-1) invivo, we determined frequencies of infection, proviral conformation,and genetic relationships between HIV-1 variants infecting naive(CD45RA⁺) and memory (CD45RO⁺) peripheral blood CD4⁺ and CD8⁺ lymphocytes. Infection of CD3⁺ CD8⁺ CD45RA⁺ cells was detected in 9 of 16 study subjects at frequencies rangingfrom 30 to 1,400 proviral copies/10⁶ cells, more frequently than CD3⁺ CD8⁺ lymphocytes expressing the RO isoform of CD45 (n = 2, 70 and260 copies /10⁶ cells). In agreement with previous studies, there was no evidencefor a similar preferential infection of CD4⁺ naive lymphocytes. Proviral sequences in both CD4⁺ and CD8⁺ lymphocyte subsets were complete, as assessed by quantitationusing primers from the long terminal repeat region spanning thetRNA primer binding site. In six of the seven study subjects investigated,variants infecting CD8⁺ lymphocytes were partially or completely genetically distinctin the V3 region from those recovered from CD4⁺ lymphocytes and showed a greater degree of compartmentalizationthan observed between naive and memory subsets of CD4⁺ lymphocytes. In two study subjects, arginine substitutions atposition 306, associated with use of the chemokine coreceptorCXCR4, were preferentially found in CD4 lymphocytes. These populationdifferences may have originated through different times of infectionrather than necessarily indicating a difference in their biologicalproperties. The preferential distribution of HIV-1 in naive CD8⁺ lymphocytes indeed suggests that infection occurred early inT-lymphocyte ontogeny, such as during maturation in the thymus.Destruction of cells destined to become CD8⁺ lymphocytes may be a major factor in the decline in CD8⁺ lymphocyte frequencies and function on disease progression andmay contribute directly to the observed immunodeficiency inAIDS.

^* Corresponding author. Mailing address: Laboratory for Clinical and Molecular Virology, University of Edinburgh, Summerhall,Edinburgh EH9 1QH, United Kingdom. Phone: 44 131 650 7927. Fax:44 131 650 7965. E-mail: Peter.Simmonds{at}ed.ac.uk.

Journal of Virology, May 2001, p. 4091-4102, Vol. 75, No. 9
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.9.4091-4102.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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