Characterization of Less Pathogenic Infectious Molecular Clones Derived from Acute-Pathogenic SHIV-89.6P Stock Virus

Abstract

For a better understanding of the acute pathogenicity of SHIV-89.6P stock virus, which induces prominent CD4 cell loss within a month after inoculation in monkeys, we have constructed four infectious molecular clones (cl 18, cl 64, cl 69, and cl 71). Cl 64, cl 69, and cl 71, like the parental virus, showed a high in vitro replication ability and a pathogenic-like effect (CD4 downmodulation) in a monkey CD4(+) cell line, whereas cl 18 showed a lower replication ability and could not downmodulate CD4. Cl 64, which has characteristics similar to those of the parental virus in vitro, was inoculated into four rhesus monkeys. All monkeys showed a plasma viral load similar to that of the parental virus with a peak at 2 weeks after inoculation. However, the viral load gradually decreased and the virus failed to cause an AIDS-like disease in infected monkeys, but it induced a strong antiviral antibody response. These results demonstrate the polyclonal nature of the parental SHIV-89.6P virus stock and demonstrate that cl 64, aside from its high replicability, may differ qualitatively from the parental virus.

Replication Properties of Clade A/C Chimeric Feline Immunodeficiency Viruses and Evaluation of Infection Kinetics in the Domestic Cat

“…The findings with chimeric FIVs may have parallels with previous work involving HIV/simian immunodeficiency virus (SHIV) chimeras (14,17,20,21,30). In these studies, initial SHIVs replicated ex vivo and in macaques but were not highly pathogenic on primary passage (20,21,30).…”

“…In these studies, initial SHIVs replicated ex vivo and in macaques but were not highly pathogenic on primary passage (20,21,30). However, pathogenicity increased upon serial in vivo passage (30), as did quasispecies diversity with respect to receptor usage and host cell range (17). Other studies have suggested a correlation with a particular threshold viral load for SHIV and the level of in vivo pathogenicity (37), which may prove to be the key as to why the high-level-replicating FIV-C36 isolate also exhibits increased pathogenicity in the periphery.…”

Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model

“…Our improved method for quantifying viral kinetics in vitrowhich depends crucially on detailed time-course information about the infection of cells in addition to that of virus (both total particle count and infectious titer) -could be applied to other viral infections. The method could likely improve the understanding of the differences in replication across different strains [25,55] or between complete and protein-deficient viruses [53,54]; the differences in viral pathogenesis [6]; and the effects of anti-viral therapies [9,13]. Quantifying the in vitro viral kinetics for viruses such as HCV [56,57], for which a convenient animal experimental model has not been established, is of particular interest.…”

“…in Table 1) were excluded when computing the SSR. Alternative fits with various weights on the infectious viral load to account for larger errors in the TCID 50 value [61], were also performed, but these did not significantly alter the extracted parameter values (Additional files 4,5,6,7,8,9). To derive the 95% confidence interval for each parameter, we employed the bootstrap method [62,63], estimating parameter values using 256 replicates of the four data sets and calculating the 2.5 and 97.5 percentiles.…”

Small Intestine CD4 + T Cells Are Profoundly Depleted during Acute Simian-Human Immunodeficiency Virus Infection, Regardless of Viral Pathogenicity

“…The genomic sequences of the two SHIVs differ by only 0.16%, resulting in a total of six amino acid changes in the products of the pol, env-gp41, and rev genes. The intravenous inoculation of rhesus macaques with #64 induces plasma viral burdens comparable to those induced by KS661 during the acute phase of infection and causes a transient reduction of the circulating CD4 ϩ T lymphocytes (10). After the acute phase, the viral loads decline to undetectable levels and the populations of CD4 ϩ T cells recover to preinfection levels.…”