Gene ew can have escaped learning The housing enclosing a viral genome Infection of a cell is followed by that once again a deadly virus is consists of a coat (capsid) made up of replication of the viral genome and syn- Floose among humans. But what many copies of a very few types of thesis of the proteins it encodes. Since are viruses, and how do they subsist and virus-specific proteins. The architecture the features of those processes depend reproduce? of the capsid is geometric; in fact, all foremost on whether DNA or RNA com- Viruses are freeloaders, parasites simple viruses exhibit helical or icosa- poses the viral genome, that property is that carry out their only function— hedral symmetry (that of a twenty-sided the basis for dividing viruses into two multiplication-only by making free regular polyhedron) or a combination major classes. use of the metabolic and biosynthetic of the two. The housing of many of the The genome of a DNA virus is pro- machinery of “host” cells, particularly more complex viruses includes an “en- cessed (transcribed and replicated) by an their machinery for protein synthesis. velope” surrounding the capsid. The infected cell in much the same way that The parasitism of some viruses is fatal envelope is very similar in structure and the cell processes its own DNA. That to host cells; that of others is benign. composition to the plasma membrane of is, the viral DNA is used as the tem- Many kinds of viruses have evolved, the host cell, containing lipids derived plate for synthesis of viral messenger each adapted to some bacterial, plant, or from the cell and virus-specific glyco- RNAs (which in turn serve as templates animal host. Of course defenses aginst proteins. for synthesis of viral proteins) and as viruses have also evolved, ranging from The processes involved in the life the template for synthesis of new vi- the restriction enzymes of bacteria to the cycle of a virus (more properly, its mul- ral DNA. However, only the simplest of immune systems of vertebrates. And, in tiplicative, or reproductive, cycle, since viruses (whether DNA or RNA) entrust the case of some animal viruses, such as viruses are not “living” organisms) in- the production of new viral components poliovirus and rabies virus, research has clude delivery of the viral genome to entirely to the normal workings of a provided vaccines that greatly strengthen the interior of a host cell, replication host cell. Instead, the genomes of most the natural immune response to viral of the viral genome, synthesis of the viruses include genes for enzymes that attack. proteins encoded by the viral genome, “reprogram” the cellular machinery to- The complete extracellular form of assembly of the newly produced viral ward preferential (sometimes exclusive) a virus is called a virion. Its compo- components into new virions, and exit processing of the viral genome. Such nents are few: a genome of nucleic of the virions from the host cell. Since reprogramming is necessary, for ex- acid, a proteinaceous housing for the the details of those processes are com- ample, to achieve rapid replication of genome, and, in certain instances, a few plex and vary from one kind of virus to the genome of a DNA virus, since a cell molecules of a virus-specific enzyme. another, only their general features are normally synthesizes DNA only in prepa- Multiplication of a virus requires repli- sketched here. ration for cell division. In addition, the cation of its genome and synthesis of Delivery of the viral genome to the genomes of most viruses include se- the proteins the genome encodes. The interior of a host cell (“infection” of quences that regulate the timing and host cell provides all of the energy and a cell) is accomplished through site- extent of gene expression. many of the biochemical needed to specific and often cell-type-specific in- Processing of the genomes of some carry out those processes. teraction of the capsid or its envelope DNA viruses does not always immedi- The genome of a virus may consist of with the cellular membrane. The site- ately follow infection. Instead the viral either one of the two nucleic acids, DNA and cell-specificities are the result of genome can become incorporated into and RNA. The nucleic acid polymer may selective interaction between viral hous- that of the host cell. There it lies la- be single- or double-stranded, linear or ing and receptors on the surface of the tent, its gene expression repressed, be- circular. Viruses with genomes of RNA cellular membrane. The mechanisms of ing passed silently through (typically) are unique: in all other organisms RNA infection are varied. For example, the many generations of daughter cells. Ul- is involved only in synthesis of proteins T4 phage infects Escherichia coli by in- timately, some stimulus triggers the exit and not also in storage of genetic infor- jection, the Semliki Forest virus infects of the viral DNA from that of the host, mation. The smaller viral genomes en- mosquito cells by receptor-mediated en- and its processing then begins. code as few as four proteins; the larger, docytosis (a normal cellular process by Three types of RNA viruses are rec- which approach the size of small bacte- which proteins enter cells), and the hu- ognized. Two are distinguished on the rial genomes, encode several hundred. man immunodeficiency virus infects T4 basis of whether the genomic RNA or its (The human genome is thought to en- lymphocytes by fusion of the viral en- complement serves as messenger RNA, code about 100,000 proteins.) evelope and the lymphocyte membrane. that is, as the template for synthesis of 48 REPRODUCTIVE PATHWAYS OF VIRUSES or RNA Viruses or Viral Proteins or Retroviruses Fig. 1. Reproduction of a virus involves replication of its genome and synthesis of the proteins encoded therein. Shown here schematically are general features of the pathways by which those processes are carried out, Each biochemical reaction is catalyzed by an enzyme; however, only the virus-specific enzymes (those not supplied by the host cell) are listed. The squares represent all viral proteins other than RNA replicase and reverse transcriptase. For simplicity the viral and cellular genomes are assumed to be single-stranded. Los Alamos Science Fall 1989 Genealogy of the AIDS Virus viral proteins. (We assume here that the genomic RNA is single-stranded; double- HIV STRUCTURE stranded genomic RNA adds only minor complications.) Encoded in the genomes Lipid of both those types of RNA viruses is an enzyme, an RNA replicase, that catalyzes the synthesis of RNA from an RNA tem- plate. (Host cells cannot supply such an enzyme because they never replicate RNA.) In the case of an RNA virus whose genomic RNA serves as messenger RNA, its RNA replicase is the first of the vi- ral proteins to be synthesized from the template of the genomic RNA. The repli- case catalyzes the synthesis first of RNA Complement to the genomic RNA and then of RNA complementary to the com- plement of the genomic RNA, that is, of RNA identical to the genomic RNA. Some of the replicas of the genomic RNA serve as genomes for daughter virions, and some serve as messenger RNA for fur- ther synthesis of viral proteins. In the case of the second type of RNA virus, the complement of the genomic RNA, and not the genomic RNA itself, serves as messenger RNA. Therefore some RNA replicase is needed initially to synthesize the complement and allow synthesis of viral proteins, including the RNA replicase. The cycle is started by entry into the cell, along with the vi- Fig. 2. The diplold genome of HIV, together with two molecules of reverse transcriptase, is housed ral genome, of a few molecules of RNA within a capsid made up of many copies of the protein p24/25. The capsid itself is encased within replicase produced during the previous an envelope made up of the glycoproteins gp120 and gp41 and a lipid bilayer derived from the reproductive cycle. Those molecules membrane of the host cell. (Adapted, with permission, from a figure in the article “AIDS in 1988” catalyze the synthesis of the comple- by Robert C. Gailo and Luc Montagnier. Scientific American, October 1988.) ment of the genomic RNA (which then serves as the template for synthesis known exception to the “central dogma” Since cells never synthesize DNA of viral proteins) and as the template of molecular genetics, which asserts from an RNA template (the reverse of for synthesis of replicas of the viral that genetic information flows from DNA transcription), a retrovirus must have genome. to RNA. The synthesized DNA, known encoded in its genome an enzyme, a The third type of RNA virus follows as proviral DNA, is incorporated into reverse transcriptase, for catalysis of an entirely different reproductive path- that of the host cell and processed by that reaction. Furthermore, since the ge- way in which neither the genomic RNA the cellular machinery under control of nomic RNA of a retrovirus is not trans- nor its complement serves as the tem- viral regulatory mechanisms. Unlike the lated into proteins, it must be accompa- plate for protein synthesis. Instead, the incorporated DNA of DNA viruses, the nied into the cell by a few molecules of genomic RNA serves as the template incorporated DNA of retroviruses is not reverse transcriptase. for synthesis of DNA. Viruses of that excised from that of the host cell before The various pathways for synthesis type, known as retroviruses, are the only processing. of viral proteins and replication of viral 50 Los Alamos Science Fall 1989 Genealogy of the AIDS Virus Fig.