title: HIV-1 interacts with human endogenous retrovirus K (HML-2) envelopes derived from human primary lymphocytes.
abstract: Human endogenous retroviruses (HERVs) are viruses that have colonized the germ line and spread through vertical passage. Only the more recently acquired HERVs, such as the HERV-K (HML-2) group, maintain coding open reading frames. Expression of HERV-Ks has been linked to different pathological conditions, including HIV infection, but our knowledge on which specific HERV-Ks are expressed in primary lymphocytes currently is very limited. To identify the most expressed HERV-Ks in an unbiased manner, we analyzed their expression patterns in peripheral blood lymphocytes using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing. We observe that three HERV-Ks (KII, K102, and K18) constitute over 90% of the total HERV-K expression in primary human lymphocytes of five different donors. We also show experimentally that two of these HERV-K env sequences (K18 and K102) retain their ability to produce full-length and posttranslationally processed envelope proteins in cell culture. We show that HERV-K18 Env can be incorporated into HIV-1 but not simian immunodeficiency virus (SIV) particles. Moreover, HERV-K18 Env incorporation into HIV-1 virions is dependent on HIV-1 matrix. Taken together, we generated high-resolution HERV-K expression profiles specific for activated human lymphocytes. We found that one of the most abundantly expressed HERV-K envelopes not only makes a full-length protein but also specifically interacts with HIV-1. Our findings raise the possibility that these endogenous retroviral Env proteins could directly influence HIV-1 replication.
  
  
  OBJECTIVE
  Here, we report the HERV-K expression profile of primary lymphocytes from 5 different healthy donors. We used a novel deep-sequencing technology (PacBio SMRT) that produces the long reads necessary to discriminate the complexity of HERV-K expression. We find that primary lymphocytes express up to 32 different HERV-K envelopes, and that at least two of the most expressed Env proteins retain their ability to make a protein. Importantly, one of them, the envelope glycoprotein of HERV-K18, is incorporated into HIV-1 in an HIV matrix-specific fashion. The ramifications of such interactions are discussed, as the possibility of HIV-1 target tissue broadening and immune evasion are considered.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Daria
authors.initials: D
authors.lastname: Brinzevich
authors.forename: George R
authors.initials: GR
authors.lastname: Young
authors.forename: Robert
authors.initials: R
authors.lastname: Sebra
authors.forename: Juan
authors.initials: J
authors.lastname: Ayllon
authors.forename: Susan M
authors.initials: SM
authors.lastname: Maio
authors.forename: Gintaras
authors.initials: G
authors.lastname: Deikus
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Chen
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Sesma
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.forename: Lubbertus C F
authors.initials: LC
authors.lastname: Mulder
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis; D020077:Endogenous Retroviruses / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D014644:Genetic Variation; D057809:HEK293 Cells; D015497:HIV-1 / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008214:Lymphocytes / Q000821:virology*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D017422:Sequence Analysis, DNA; D015302:Simian Immunodeficiency Virus / Q000378:metabolism; D059467:Transcriptome; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D014759:Viral Envelope Proteins