Colony collapse disorder (CCD) has caused such a profound drop in honeybee populations that even the U.S. Congress is addressing the issue: Senator Jeff Merkley (D-Oregon) has proposed the Pollinator Recovery Act to preserve pollinator habitat. The rapid decline in these important pollinators affects the economy and agriculture of bee-deprived regions. Hive disappearances have been described by beekeepers before, but the large number of countries affected, and the duration of the phenomenon, have motivated scientists to concentrate on this apiary anomaly.
While there is no universally-accepted cause of CCD, a number of pathogenic viruses have been associated with the death of entire colonies, with geographically distinct picorna-like viruses from the Dicistroviridae and Iflaviridae families playing a large role. In the United States, the non-enveloped, RNA virus, Israeli acute paralysis virus (IAPV), infects every stage and caste of honeybees and is strongly associated with CCD. New research now available in the Journal of Virology investigates the structure of IAPV.
Knowing the virus structure can provide valuable information such as what are the size limitations of the virus, where are the receptors for attachment, or how does the virus uncoat its genome. First author Edukondalu Mullapudi and senior author Pavel Plevka hoped to learn some of these biological aspects from determining the structure of IAPV.
To begin their studies, the scientists propagated the virus in honeybee larvae to generate native structures. The crystal structure of the purified virus showed the viral capsid, composed of VP1, VP2, VP3, and VP4 capsid proteins, has icosahedral symmetry. The IAPV surface topology differs quite a bit from the previously crystallized dicistrovirus, CrPV, and somewhat from the dicistrovirus TrV (see figure, right). IAPV shares only about 25% sequence similarity with each of these viruses, which are more closely related to each other, demonstrating the importance of determining the structure independent from sequence homology.
Although native virions were purified for crystallization, some of the crystals formed were from capsid protomers, the repeating capsid subunit consisting of several capsid proteins, rather than intact capsid. These protomers lacked VP4, which is released along with the viral genome during mammalian picornavirus uncoating. The authors speculate that the crystallized protomers represent the remnant capsid particles of uncoated virions, and that VP4 may play a similar role in IAPV uncoating. This adds a valuable clue to the dicistrovirus genome delivery mechanism, which has previously remained unstudied.
The IAPV structure is similar to vertebrate picornaviruses, which includes enteroviruses, hepatoviruses, and rhinoviruses. Some picornaviruses can be treated with compounds that inhibit their uncoating; the compound interacts with a hydrophobic pocket in the V1 capsid protein. Comparing the IAPV VP1 structure to that of PV-1 reveals no hydrophobic pocket in the IAPV structure (see figure, left), suggesting IAPV is unlikely to inhibited by similar compounds.
Defining the IAPV structure and life cycle may help scientists design inhibitors for these CCD-associated pathogens. While this may not answer all aspects of these mysterious events (such as: why are there no bee carcasses from collapsed colonies?), protecting these hives remains the current top priority. Learning the IAPV structure may have ruled out one class of inhibitors, but it will also allow scientists to examine new methods to manipulate viral biology and stem the spread of IAPV.
-- Julie Wolf