Ability of Hyaluronidase 2 To Degrade Extracellular Hyaluronan Is Not Required for Its Function as a Receptor for Jaagsiekte Sheep Retrovirus

Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109-1024, USA.
Journal of Virology (Impact Factor: 4.44). 05/2007; 81(7):3124-9. DOI: 10.1128/JVI.02177-06
Source: PubMed


Jaagsiekte sheep retrovirus (JSRV) uses hyaluronidase 2 (Hyal2) as a cell entry receptor. By making inactivating mutations to the catalytic residues of human Hyal2, we found that hyaluronidase activity was dispensable for its receptor function. The affinities of the JSRV envelope glycoprotein for Hyal2 and the Hyal2 mutant were similar, and hyaluronan did not block either high-affinity interaction or virus infection. While generating the Hyal2 mutant, we discovered that our previous analysis of the hyaluronidase activity of Hyal2 was affected by a contaminating hyaluronan lyase, which we have identified as the occlusion-derived baculovirus E66 protein of the recombinant baculovirus used to produce Hyal2. We now report that purified human Hyal2 is a weak acid-active hyaluronidase.

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Available from: Vladimir Vigdorovich,
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    • "The hyaluronidase activity of HYAL-2 is not required for its retrovirus receptor function, as demonstrated by inactivating mutations of the catalytic residues, which do not affect virus-receptor interaction (Vigdorovich et al., 2007). The Jaagsiekte Sheep RetroVirus-envelope mediated fusion requires a low pH and the cytoplasmic tail of the envelope negatively regulates the fusion activity (Cote et al., 2011). "
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    ABSTRACT: Sheep and goats are widely infected by oncogenic retroviruses, namely Jaagsiekte Sheep RetroVirus (JSRV) and Enzootic Nasal Tumour Virus (ENTV). Under field conditions, these viruses induce transformation of differentiated epithelial cells in the lungs for Jaagsiekte Sheep RetroVirus or the nasal cavities for Enzootic Nasal Tumour Virus. As in other vertebrates, a family of endogenous retroviruses named endogenous Jaagsiekte Sheep RetroVirus (enJSRV) and closely related to exogenous Jaagsiekte Sheep RetroVirus is present in domestic and wild small ruminants. Interestingly, Jaagsiekte Sheep RetroVirus and Enzootic Nasal Tumour Virus are able to promote cell transformation, leading to cancer through their envelope glycoproteins. In vitro, it has been demonstrated that the envelope is able to deregulate some of the important signaling pathways that control cell proliferation. The role of the retroviral envelope in cell transformation has attracted considerable attention in the past years, but it appears to be highly dependent of the nature and origin of the cells used. Aside from its health impact in animals, it has been reported for many years that the Jaagsiekte Sheep RetroVirus-induced lung cancer is analogous to a rare, peculiar form of lung adenocarcinoma in humans, namely lepidic pulmonary adenocarcinoma. The implication of a retrovirus related to Jaagsiekte Sheep RetroVirus is still controversial and under investigation, but the identification of an infectious agent associated with the development of lepidic pulmonary adenocarcinomas might help us to understand cancer development. This review explores the mechanisms of induction of respiratory cancers in small ruminants and the possible link between retrovirus and lepidic pulmonary adenocarcinomas in humans.
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    • "Its N terminus was shown to be sufficient to traffic proteins to the inner nuclear membrane (Hong et al., 1997). The ODV-E66 protein has homology to hyaluronidases, and it was identified as a contaminating protein with hyaluronidase activity during purification of a human hyaluronidase from baculovirus-infected cells (Vigdorovich et al., 2007). In 2011, it was discovered that AcMPNV-infected cells contained chondroitinase activity in the cell supernatant, which was identified as an N-terminally truncated form of ODV-E66 (Sugiura et al., 2011). "
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    Virology 02/2015; 479-480. DOI:10.1016/j.virol.2015.01.027 · 3.32 Impact Factor
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    • "In CiBV particles, gene products having similarity to occlusion-derived virus (ODV) components of baculovirus envelopes were also identified, namely the per os infectivity factors P74, PIF-1 and PIF-2 as well as ODV-E56 and two variants of ODV-E66 (Table 1). ODV-E51 was proposed to play a role in ODV morphogenesis (Braunagel & Summers, 2007), and ODV- E66 has a hyaluronan lyase activity thought to be important for the penetration of extracellular barriers to access host cells (Vigdorovich et al., 2007). All the corresponding transcripts increased at the virion formation stage: p74 "
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