Enhancement of equine infectious anemia virus virulence by identification and removal of suboptimal nucleotides.

This research paper discusses how the virulence, or disease-causing potential, of the equine infectious anemia virus (EIAV) was increased by identifying and eliminating suboptimal nucleotides from the virus’s genetic material.

About the EIAV and Its Variants

The equine infectious anemia virus (EIAV) is a lentivirus that leads to equine infectious anemia, a serious and often fatal disease among horses. This paper studies two forms of the EIAV: an avirulent, or non-disease-causing form called EIAV(UK), and a pathogenic or disease-causing one referred to as EIAV(PV).

• The researchers initially created a hybrid of these two forms by replacing some genetic sequences from EIAV(UK) with sequences from EIAV(PV).
• Despite these changes, horses injected with the chimeric clone still developed the disease less frequently than those with EIAV(PV).

The Role of Suboptimal Nucleotides

Suboptimal nucleotides refer to DNA sequences that aren’t exactly “ideal” or fully effective. In this case, such suboptimal sequences in EIAV(UK) resulted in lower virulence. Two discrepancies were specifically identified between the EIAV(UK) and EIAV(PV):

• A 68-base pair duplication in the 3′ Long Terminal Repeat (LTR) region of the proviral genome (the DNA form of the virus after it has integrated into the host cell’s genome).
• In the second exon of the viral “rev” gene, there was a substitution of arginine (R) instead of tryptophan (W) at the 103rd position.

Enhancing Virulency

The researchers were able to enhance the EIAV(UK) virus’s virulence by eliminating these suboptimal nucleotides:

• The 68 base pair duplication was naturally eliminated rapidly in horses who received the EIAV(UK).
• The 103rd position arginine was naturally replaced by tryptophan within the viral population in those horses.
• Manually removing these variant sequences from EIAV(UK) resulted in a disease potential that was equivalent to EIAV(PV).

The data suggest that these suboptimal sequences – the 68 base pair duplication and arginine in place of tryptophan, limit the virus’s ability to generate high amounts of viral RNA during the acute infection phase thus reducing its virulence.