Viral Phenotypes and Antibody Responses in Long-Term Survivors Infected with Attenuated Human Immunodeficiency Virus Type 1 Containing Deletions in the nef and Long Terminal Repeat Regions

Author:

Verity Erin E.123,Zotos Dimitra34,Wilson Kim3,Chatfield Catherine2,Lawson Victoria A.2,Dwyer Dominic E.5,Cunningham Anthony5,Learmont Jennifer6,Dyer Wayne6,Sullivan John6,Churchill Melissa2,Wesselingh Steven L.27,Gabuzda Dana89,Gorry Paul R.278,McPhee Dale A.123

Affiliation:

1. Department of Microbiology, Monash University, Clayton, Victoria, Australia

2. Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia

3. National Serology Reference Laboratory Australia, St Vincent's Institute, Fitzroy, Victoria, Australia

4. School of Biological and Chemical Sciences, Deakin University, Burwood, Victoria, Australia

5. Centre for Virus Research, Westmead Millenium Institute, Westmead, New South Wales, Australia

6. Australian Red Cross Blood Service, Sydney, New South Wales, Australia

7. Department of Medicine, Monash University, Melbourne, Victoria, Australia

8. Dana-Farber Cancer Institute, Boston, Massachusetts

9. Department of Neurology, Harvard Medical School, Boston, Massachusetts

Abstract

ABSTRACT The Sydney Blood Bank Cohort (SBBC) consists of eight blood transfusion recipients infected with nef -attenuated human immunodeficiency virus type 1 (HIV-1) acquired from a single donor. Here, we show that viral phenotypes and antibody responses differ considerably between individual cohort members, despite the single source of infection. Replication of isolated virus varied from barely detectable to similar to that of the wild-type virus, and virus isolated from five SBBC members showed coreceptor usage signatures unique to each individual. Higher viral loads and stronger neutralizing antibody responses were associated with better-replicating viral strains, and detectable viral replication was essential for the development of strong and sustained humoral immune responses. Despite the presence of strong neutralizing antibodies in a number of SBBC members, disease progression was not prevented, and each cohort member studied displayed a unique outcome of infection with nef -attenuated HIV-1.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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