Further Evidence that Human Endogenous Retrovirus K102 is a Replication Competent Foamy Virus that may Antagonize HIV-1 Replication



Marian P. Laderoute*, #, 1, 4, Louise J. Larocque$, 1, Antonio Giulivi2, 4, Francisco Diaz-Mitoma3, 4
1 Bloodborne Pathogens Division, Blood Zoonotics Unit, Public Health Agency of Canada, Ottawa, Ontario Canada
2 Division of Hematopathology and Transfusion Medicine, The Ottawa Hospital, Ottawa, Ontario Canada
3 The Advanced Medical Research Institute of Canada, Sudbury, Ontario Canada
4 Department of Pathology and Laboratory Medicine, The University of Ottawa, Ottawa, Ontario Canada


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© Laderoute et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the P.O. Box 76045, Aylmer Ouest, Gatineau, QC, J9H 6W0, Canada; E-mail: hervk102@bell.net
# Recently Retired from Immune System Management Clinic and Lab, Ottawa, Ontario Canada;
$ Presently at the Centre for Biologics Evaluation, Health Canada, Ottawa, Ontario Canada


Abstract

Objective:

The goals of the research were to determine if a foamy effect on macrophages was due to human endogenous retrovirus K102 (HERV-K102) replication, and to further address its potential significance in HIV-1 infection.

Methods:

An RT-PCR HERV-K HML-2 pol method was used to screen the unknown HERV, and isolated bands were sent for sequencing. Confirmation of RNA expression was performed by a real time quantitative PCR (qPCR) pol ddCt method. Rabbit antibodies to Env peptides were used to assess expression by immunohistology and processing of Env by western blots. A qPCR pol ddCt method to ascertain genomic copy number was performed on genomic DNA isolated from plasma comparing HIV-1 exposed seronegative (HESN) commercial sex workers (CSW) to normal controls and contrasted with HIV-1 patients.

Results:

HERV-K102 expression, particle production and replication were associated with foamy macrophage generation in the cultures of cord blood mononuclear cells under permissive conditions. A five-fold increased HERV-K102 pol genomic copy number was found in the HESN cohort over normal which was not found in HIV-1 positive patients (p=0.0005).

Conclusions:

This work extends the evidence that HERV-K102 has foamy virus attributes, is replication competent, and is capable of high replication rate in vivo and in vitro. This may be the first characterization of a replication-competent, foamy-like virus of humans. High particle production inferred by increased integration in the HESN cohort over HIV-1 patients raises the issue of the clinical importance of HERV-K102 particle production as an early protective innate immune response against HIV-1 replication.

Keywords: HERV-K102, HIV-1, HML-2 type 1, DNA genomes, foamy virus, HESN, innate immunity, foamy macrophages.