Description

For all viruses, the structure of the viral particle (virion) in part reflects the fundamental requirements imposed by the need for propagation. These requirements include incorporation of the genome into particles that are stable outside of cells, recognition of and entry into appropriate host cells, replication of the genome, and the translation of viral messenger RNA to yield new viral proteins. Retroviruses are enveloped RNA viruses, a complex group with several common features. Enveloped RNA viruses contain proteins that carry out five basic functions, condensation of the genome into an RNA protein complex, packaging of this complex in a protein shell, enclosure of the shell in a lipid membrane, or envelope, modification of the envelope by addition of surface proteins that recognize cellular receptors and for negative strand viruses and retroviruses, copying of the RNA in the newly infected cell.

Morphology of Virions

Many enveloped viruses in fact are more complicated, with two or more proteins sharing each function, and others are simpler, with one protein carrying out two or three functions. The simpler enveloped viruses provide useful paradigms to help understand aspects of retroviral structure. Until the successful crystallization and X-ray diffraction work on spherical viruses in the last decade, structural information was gained largely by fractionation of the components of purified viruses, by electron microscopy, and indirectly by genetic analysis. For the many viruses for which useful crystals have not been obtained, these techniques remain the cornerstone upon which inferences about structure are built. The first substantially pure preparations of retroviruses became available in the 1960s, for the Avian Sarcoma or Leukosis Viruses (ASLVs) and the Murine Leukemia Viruses (MLVs), which were the most widely studied retroviruses until the advent of Human Immunodeficiency Virus (HIV) and that the reverse transcriptase itself, as well as the protease necessary for processing of the precursor, is translated as a precursor also containing the structural proteins. The much later observation that the virus carries with it the enzyme catalyzing integration of viral DNA into host chromosomes further solidified the view of retroviral structure and replication. Eventually extended to HIV and other viruses.

RNPs within the Virion

The length of each rod-like RNP correlates with the length of each vRNA segment. Although the morphology of the purified RNPs has been well characterized, the conformation of RNPs inside virions had been largely unknown for a long time. When virions were examined by using negative staining Electron Microscopy (EM), a continuous strand of 7–8 nm in diameter, which was regularly packed in the form of a helix, was observed within disrupted virions. Although the strands were observed only at a low frequency, they were the sole structure clearly visualized by using negative-staining EM. Therefore, it was proposed that RNPs exist as a single continuous helix, which would be fragmented into multiple rod-like RNPs during the purification process of RNPs. Later, however, it was demonstrated by use of negative-staining, that the continuous helix found within disrupted virions was a layer of M1 proteins underneath the lipid envelope. The RNPs are always suspended from the top of the budding virions and are oriented perpendicular to the budding tip. Many transversely sectioned budding virions contain eight RNPs, in which a central RNP is consistently surrounded by seven others. Serial transverse ultrathin sections of whole budding virions have revealed that the eight RNPs within a virion differ in length, suggesting that the budding virion contains different kinds of vRNAs. Filamentous virions also contain eight RNPs arranged in this distinct pattern. Interestingly, the eight RNPs are confined to the top of the filamentous virion and the reminder of the filamentous virion is empty, indicating that such filamentous virions do not randomly incorporate multiple sets of eight RNPs. Recent analyses of purified virions confirmed that they contain eight RNPs arranged in a distinct. Furthermore, the RNPs are restricted to one end of the filamentous particles that are released from infected cells, which is consistent with the observations made by using ultrathin-section EM of budding virions. Thus, virions, regardless of their shape, incorporate an organized set of eight RNPs.