Retroviruses
I Retroviridae: General Features
• Midsized viruses with an enveloped capsid containing two copies of a single-stranded (+) RNA genome, transfer RNA (tRNA), reverse transcriptase, integrase, and protease.
• Two human pathogens—human immunodeficiency virus (HIV) and human T lymphotropic virus (HTLV)—are retroviruses.
1. All retroviral genomes contain three genes—gag, pol, and env—and are flanked by long-terminal repeats (Table 26-1).
TABLE 26-1
Retrovirus Genes and Their Function
| Gene | Virus | Function |
| gag | All | Group-specific antigen: core and capsid proteins |
| int | All | Integrase |
| pol | All | Polymerase: reverse transcriptase, protease, integrase |
| pro | All | Protease |
| env | All | Envelope: glycoproteins |
| tax | HTLV | Transactivation of viral and cellular genes |
| tat | HIV-1 | Transactivation of viral and cellular genes |
| rex | HTLV | Regulation of RNA splicing and promotion of export to cytoplasm |
| rev | HIV-1 | Regulation of RNA splicing and promotion of export to cytoplasm |
| nef | HIV-1 | Alteration of cell activation signals; progression to AIDS (essential) |
| vif | HIV-1 | Virus infectivity, promotion of assembly, blocks a cellular antiviral protein |
| vpu | HIV-1 | Facilitates virion assembly and release, decrease of cell surface CD4 |
| vpr (vpx*) | HIV-1 | Transport of complementary DNA to nucleus, arresting of cell growth |
| LTR | All | Promoter, enhancer elements |
From Murray PR, Rosenthal KS, Pfaller MA: Medical Microbiology, 6th ed. Philadelphia, Mosby, 2009, Table 64-2.
2. Complex retroviruses, such as HIV, have several other genes encoding auxiliary and regulatory proteins (e.g., nef, tat, and rev)
B Key HIV proteins (Fig. 26-1)
26-1 Genome structure of human retroviruses: (A) HTLV-1 and (B) HIV. The basic retrovirus genome consists of the long terminal repeat (ltr) group–specific antigen (capsid proteins)(gag)-enzymes(polymerase, integrase, protease)(env) and the glycoproteins (env). Complex retroviruses, such as HIV have additional proteins that enhance their virulence. These are described in Table 26-1. (Redrawn from Belshe RB: Textbook of Human Virology, 2nd ed. St Louis, Mosby, 1991. In Murray PR, Rosenthal KS, Pfaller MA: Medical Microbiology, 6th ed. Philadelphia, Mosby, 2009, Fig. 64-4.)
1. Major envelope glycoprotein consists of two associated proteins: an attachment protein (HIV gp120) and transmembrane fusion protein (HIV gp41) both cleaved from gp160 precursor.
2. Three enzymes are carried within the nucleocapsid: reverse transcriptase, integrase, and protease.
3. Matrix protein (HIV p17) forms a layer underlying the envelope.
4. Nucleocapsid protein (HIV p24) forms the outer layer of the virion core, and detection in blood indicates infection.
• Binding of viral gp120/gp41 to CD4 and a chemokine coreceptor is required for HIV infection of cells.
• Reverse transcriptase carried in the virion synthesizes a complementary DNA (cDNA) from viral genome, forming an RNA-DNA hybrid. The same enzyme then degrades the RNA strand and synthesizes a complementary DNA strand, forming double-stranded viral DNA.
• Viral integrase catalyzes integration of viral DNA into host nuclear DNA, forming provirus.
3. Viral messenger RNA (mRNA) and genome replication
• Host DNA-dependent RNA polymerase transcribes a full-length (+) RNA copy of the integrated genome and several shorter mRNA copies for individual proteins and polyproteins.
• After synthesis of viral proteins, nucleocapsids containing two copies of genome associate with glycoprotein modified plasma membrane and bud off.
• After budding, protease cleaves gag-pol polyprotein to produce mature (cone-shaped) nucleocapsid and functional integrase and reverse transcriptase enzymes.
