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Retroviral Study Reveals Potential for Influencing HIV Replication

Tuesday, May 6, 2014

Scientists from the Icahn School of Medicine at Mount Sinai in New York City and the MRC National Institute for Medical Research in London published a paper using Single Molecule, Real-Time (SMRT®) Sequencing to gain a better understanding of how human endogenous retroviruses may be interacting with HIV infection. They pursued a new avenue of research that could shed light on how to interfere with HIV replication.

HIV-1 interacts with HERV-K (HML-2) Envelopes derived from human primary lymphocytes” was recently published in the Journal of Virology, a publication of the American Society for Microbiology. Daria Brinzevich and George R. Young were lead authors on the work.

The scientists conducted a study uniquely suited to the extremely long reads provided by the PacBio® platform, noting that this technology was needed to accurately parse the complexity in expression among a specific group of human endogenous retroviruses (HERVs). “Applied to the sequencing of PCR products, PacBio reads maintain the entire product as an uninterrupted sequence, allowing reliable identification against reference libraries with the equivalent levels of similarity as those of HERV-Ks,” the authors write.

In this project, the scientists dug deeper into evidence that expression of the endogenous retroviruses that make up almost 5% of the human genome is upregulated when a person is infected with HIV-1. “HIV-1 infection in human cells is equivalent to a co-infection by several retroviruses,” they explain. They used SMRT Sequencing to analyze the expression profiles of the HERV-K group of retroviruses in lymphocytes from five healthy people.

The team found nearly 4,000 HERV-K sequences in these lymphocytes, compared to a previous study from other scientists that found fewer than 1,000 of these sequences in 11 samples. They posit that the higher number seen here reflects the greater sensitivity of PacBio sequencing as well as the difference in cell types analyzed.

In all, the authors identified more than 30 different transcripts for HERV-K envelopes, including two that produce full-length proteins — one of which was found to incorporate into HIV-1 particles. “These findings imply that some HERV-Ks interact specifically with HIV possibly shaping the properties of the lentivirus,” they write. “Future studies are needed to determine the extent of their influence on the HIV-1 life cycle and whether their expression can be harnessed to hinder HIV-1 replication.”

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