Rama Thakallapally, Carla Kuiken
T10, MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545
Since last year's edition of this section, a few new attenuated SIVs and SHIVs have been added to the collection. We have attempted to include all strains represented in the literature; i f there are any that are not included, we would very much appreciate hearing about them; we will make sure they will be added in the next edition of the Compendium. All isolates have a separate color code, so that identifying the structure and composition of the genome of the strains can be done at a glance. Suggestions to make this section more useful are welcome.
In Figures 1-3 we present an overview of the virus strains that are frequently used in these studies and their derivation. A distinction must be made between strains used for vaccination, which obviously must be non-pathogenic, and strains used for challenge, which tend to be pathogenic. Some strains have been used both as vaccine and as challenge strains. Pathogenicity is relative, and depends on the virus, the host species, and the individual host. For example, SIVsm is not pathogenic in its natural host, the sooty mangabey, but can be highly pathogenic to macaques.
SIVmac viruses are used most extensively in these studies. The SIVmac isolates 251 and 32H both have a less pathogenic counterpart, clones 1A11 and C8, respectively. These clones are genetically very similar to the quasispecies they were derived from, but they have one or more attenuating genetic deletions. Another important SIVmac isolate, 239, is a clonal isolate from rhesus monkey #239. SIVmac239 is pathogenic, but a long series of reduced- or non-pathogenic strains with varying number of deletions in the genome has been derived from it. These strains cover a spectrum of pathogenicity, ranging from highly pathogenic to apparently non-infectious (unable to replicate in the host) (Desrosiers et al. 1998). It has recently become apparent that monkeys infected with SIVmac239-D3, in the lower mid range of the pathogenicity spectrum, do develop AIDS after several years (Cohen 1997). Two macrophage-tropic variants have also been derived from SIVmac-239: SIVmac316 and 17E (see Figure 1a).
SIVsm isolates can be highly pathogenic to macaques. Pathogenic challenge stocks in this group are usually bulk (rather than clonal) isolates, passaged in one of several macaques. Genetic clones of this group (such as SIVsmH4) tend to be much less pathogenic. An important and highly pathogenic strain is SIVsmPBj14, which kills a majority of infected macaques at primary infection, within a few weeks; monkeys that survive primary infection usually die of an AIDS-like illness within two years. Other isolates that have been used as challenge stocks are B670 and E660. Derivation of commonly used isolates from this group is shown in Figure 1b.
In recent years the repertoire of non-pathogenic vaccine strains has been extended by the creation of artificially attenuated virus variants. This is usually done either by creating stop codons in non-vital sections, or deleting sections from the genome of a virulent strain. Figure2 shows a schematic representation of attenuated SIV strains. The diagram shows where changes have been made or documented with respect to the wild type.
Figure 3 gives an overview of SHIV strains that are presently in use in the vaccine field, and indicates which section of the genomes are derived from HIV-1 (and which strain of HIV-1), and which from a SIV strain.
We gratefully acknowledge the help of Drs. Jim Bradac and Alan Schultz from NIAID for invaluable background information and helpful suggestions.
Figure 3. Schematic representation of common attenuated SIV strains used in vaccine research. Deletions are indicated in white, mutations are shown as black lines. Mutations may include insertion or deletion of a stop codon.
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