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Comparative Genomics Reveals Differences in Lion FIV Strains

This article has been updated to include comments from one of the study's authors.
NEW YORK (GenomeWeb News) – New research comparing lion feline immunodeficiency virus genomes with FIV strains from other cats suggests the virus varies between — and within — feline species.
Researchers from the National Cancer Institute-Frederick in Maryland, and Colorado and Washington State Universities, along with African consultants, sequenced the genomes of two distinct FIV subtypes isolated from wild lions in Tanzania and Botswana. Their results, published online last night in the journal BMC Genomics, may help scientists understand the virus’ pathogenesis and evolution as well as that of similar viruses such as HIV.
FIV is a lentivirus that affects both wild and domesticated cat species, though the severity of the disease varies by species. In domestic cats, for example, a strain called FIVFca causes a serious illness characterized by flu-like symptoms, weight loss, and compromised immunity that increases the animal’s susceptibility to rare cancers, infections, and other opportunistic diseases. But in lions and pumas, the symptoms appear to be less serious, though FIV is associated with altered immune cell profiles in both animals.
Since FIV is the only widespread, naturally occurring virus causing a disease similar to HIV-AIDS, it may serve as a useful model for human infections, senior author Stephen O’Brien, a National Cancer Institute geneticist, told GenomeWeb Daily News today.
In an effort to understand FIV’s natural history in the cat family, O’Brien and his team isolated FIV viruses from lions in Tanzania’s Serengeti National Park and the Okavango Delta in Botswana and sequenced the full length of the proviruses — dubbed FIVPle subtypes B and E, respectively.
By comparing these FIV subtypes — each roughly 9,900 base pairs long — to puma, Pallas, and domestic cat FIV strains from GenBank using pair-wise Blast comparisons as well as multiple sequence alignments with ClustalX and the REVTRANS program, they identified both conserved and highly divergent regions within FIV.
For instance, while the pol ORF — which codes for important viral enzymes — is well conserved, ORFs called vif, orfA, and env — which code for a viral replication accessory protein, a possible transcription factor targeting protein, and a viral envelope component, respectively — are highly divergent. O’Brien’s group also found unexpected variation within the env gene between the two lion FIV subtypes B and E.
Unexpectedly, the patterns they found suggest that the closest relative to lion FIV actually infects the Asian Pallas cat, which lives in Mongolia. Although there are about 20 cat species in Asian, O’Brien said that the Pallas cat is the only one shown to carry FIV. The tremendous diversity in the env ORF is less surprising, he adds, since the viral envelope proteins mutate quickly to avoid the animals’ immune system.
Eventually, O’Brien and others hope to sequence FIV strains from all exotic cats that carry the virus, an approach that should help them further understand the viruses evolution and recombination — events that contribute to its virulence and pathogenicity.
“This study demonstrates the necessity of whole-genome analysis to complement population/gene-based studies, which are of limited utility in uncovering complex events such as recombination that may lead to functional differences in virulence and pathogenicity,” the authors wrote.

Still, O’Brien emphasized the importance of collaborating with experts in other fields, such as ecology, to interpret and contextualize their genomics results since, he says,“Most genomics people don’t really see anything besides the DNA sequence.”

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