Fate of an Infectious ERV in Wild and Domestic Cats

Endogenous retroviruses (ERVs) of domestic cats (ERV-DCs) are one of the youngest feline ERV groups in domestic cats (Felis silvestris catus); some members are replication competent (ERV-DC10, ERV-DC18, and ERV-DC14), produce the antiretroviral soluble factor Refrex-1 (ERV-DC7 and ERV-DC16), or can generate recombinant feline leukemia virus (FeLV). Here, we investigated ERV-DC in European wildcats (Felis silvestris silvestris) and detected four loci: ERV-DC6, ERV-DC7, ERV-DC14, and ERV-DC16. ERV-DC14 was detected at a high frequency in European wildcats; however, it was replication defective due to a single G → A nucleotide substitution, resulting in an E148K substitution in the ERV-DC14 envelope (Env). This mutation results in a cleavage-defective Env that is not incorporated into viral particles. Introduction of the same mutation into feline and murine infectious gammaretroviruses resulted in a similar Env dysfunction. Interestingly, the same mutation was found in an FeLV isolate from naturally occurring thymic lymphoma and a mouse ERV, suggesting a common mechanism of virus inactivation. Refrex-1 was present in European wildcats; however, ERV-DC16, but not ERV-DC7, was unfixed in European wildcats. Thus, Refrex-1 has had an antiviral role throughout the evolution of the genus Felis, predating cat exposure to feline retroviruses. ERV-DC sequence diversity was present across wild and domestic cats but was locus dependent. In conclusion, ERVs have evolved species-specific phenotypes through the interplay between ERVs and their hosts. The mechanism of viral inactivation may be similar irrespective of the evolutionary history of retroviruses. The tracking of ancestral retroviruses can shed light on their roles in pathogenesis and host-virus evolution

Study area.

<p>Mountain massifs in the study area within the Spanish Pyrenees. 1. Ori; 2. Ezkaurre; 3. Larra – Peña Forca; 4. Bixaurín; 5. Anayet; 6. Biñamala; 7. Monte Perdido; 8. Liena; 9. Punta Suelsa; 10. Posets; 11. Maladeta; 12. Cotiella; 13. Sierra Ferrera; 14. Turbón. Grey indicates the area directly managed by the regional administration in Aragon.</p

IKC-affected female whit many flies around the head.

<p>IKC-affected female whit many flies around the head.</p

Adult female and kid affected with IKC.

<p>Adult female and kid affected with IKC.</p

Detection of <i>Mycoplasma conjunctivae</i> based on the ages and sexes of the animals checked (N = 105, 2006–2008).

<p>Detection of <i>Mycoplasma conjunctivae</i> based on the ages and sexes of the animals checked (N = 105, 2006–2008).</p

Stages lesion of IKC in Pyrenean chamois during 2006–2008 outbreak.

<p>Pictures show animals with different levels of disease severity<b>. A)</b> Purulent ocular lacrimation and mild corneal opacity (stage II). <b>B)</b> Corneal opacity (stage III). <b>C)</b> Late stage of IKC, with purulent exudation, evident conjunctivitis and corneal perforation (stage IV)<b>. D)</b> Animal without lacrimation that had chronic corneal lesions showing the face without hair.</p

Age and sex of chamois analyzed in the Aragonese and Navarrese Pyrenees with infectious keratoconjunctivitis during the outbreak (N = 105, 2006–2008).

<p>Age and sex of chamois analyzed in the Aragonese and Navarrese Pyrenees with infectious keratoconjunctivitis during the outbreak (N = 105, 2006–2008).</p

Age and sex of chamois found dead in the Aragonese Pyrenees (N = 471, 2006–2010).

<p>Age and sex of chamois found dead in the Aragonese Pyrenees (N = 471, 2006–2010).</p

Pyrenean chamois found dead in the Aragonese and Navarrese Pyrenees.

<p>Pyrenean chamois found dead in the Aragonese and Navarrese Pyrenees.</p

Spatial distribution over Pyrenean massifs of IKC-outbreak locations for years: A) 2006, B) 2007 and C) 2008.

<p>Spatial distribution over Pyrenean massifs of IKC-outbreak locations for years: A) 2006, B) 2007 and C) 2008.</p