Possible role for cellular karyopherins in regulating polyomavirus and papillomavirus capsid assembly.
نویسندگان
چکیده
Polyomavirus and papillomavirus (papovavirus) capsids are composed of 72 capsomeres of their major capsid proteins, VP1 and L1, respectively. After translation in the cytoplasm, L1 and VP1 pentamerize into capsomeres and are then imported into the nucleus using the cellular alpha and beta karyopherins. Virion assembly only occurs in the nucleus, and cellular mechanisms exist to prevent premature capsid assembly in the cytosol. We have identified the karyopherin family of nuclear import factors as possible "chaperones" in preventing the cytoplasmic assembly of papovavirus capsomeres. Recombinant murine polyomavirus (mPy) VP1 and human papillomavirus type 11 (HPV11) L1 capsomeres bound the karyopherin heterodimer alpha2beta1 in vitro in a nuclear localization signal (NLS)-dependent manner. Because the amino acid sequence comprising the NLS of VP1 and L1 overlaps the previously identified DNA binding domain, we examined the relationship between karyopherin and DNA binding of both mPy VP1 and HPV11 L1. Capsomeres of L1, but not VP1, bound by karyopherin alpha2beta1 or beta1 alone were unable to bind DNA. VP1 and L1 capsomeres could bind both karyopherin alpha2 and DNA simultaneously. Both VP1 and L1 capsomeres bound by karyopherin alpha2beta1 were unable to assemble into capsids, as shown by in vitro assembly reactions. These results support a role for karyopherins as chaperones in the in vivo regulation of viral capsid assembly.
منابع مشابه
Chaperone-mediated in vitro disassembly of polyoma- and papillomaviruses.
Hsp70 chaperones play a role in polyoma- and papillomavirus assembly, as evidenced by their interaction in vivo with polyomavirus capsid proteins at late times after virus infection and by their ability to assemble viral capsomeres into capsids in vitro. We studied whether Hsp70 chaperones might also participate in the uncoating reaction. In vivo, Hsp70 co-immunoprecipitated with polyomavirus v...
متن کاملChaperone-mediated in vitro assembly of Polyomavirus capsids.
The polyomavirus coat protein viral protein 1 (VP1) has the intrinsic ability to self-assemble in vitro into polymorphic capsid-like structures on addition of calcium. In contrast, polyomavirus assembly in vivo is rigorously controlled, such that virions of uniform size are formed only in the cell nucleus. During viral infection, the 72 kDa cellular chaperone heat shock cognate protein (hsc70) ...
متن کاملHuman papillomavirus genotype 16 pseudovirus production and purification in HEK-293FT cells
Introduction: Human papillomavirus (HPV) is the main causative agent of cervical cancer worldwide leading to a big health problem, especially in the developing countries. Among 14 common high-risk genotypes, HPV16 accounts for more than 50% of all cervical cancers. The current prophylactic vaccines against HPV infection are based on L1 protein. Due to some drawbacks in the current vaccines such...
متن کاملConstruction and evaluation of human papillomavirus genotype 18 pseudovirions
Introduction: Cervical cancer is the second most common cancer in women worldwide and the role of human papillomavirus (HPV) has been proved in its etiology. The currentley available L1-capsid-protein-based vaccine is highly immunogenic and very high titers of serum antibodies can be obtained by its injection, but unfortunately it is restricted to only a few HPV genotypes and is relatively expe...
متن کاملIn vivo and in vitro association of hsc70 with polyomavirus capsid proteins.
Members of the 70-kDa family of cellular stress proteins assit in protein folding by preventing inappropriate intra- and intermolecular interactions during normal protein synthesis and transport and when cells are exposed to a variety of environmental stresses. During infection of A31 mouse fibroblasts with polyomavirus, the constitutive form of hsp70, hsc70, coimmunoprecipitated with all three...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of virology
دوره 82 20 شماره
صفحات -
تاریخ انتشار 2008