Biomedical subjects

Jenny L Anderson

Publications and source records attributed to Jenny L Anderson.

4 recordsLinked to original sources

PubMed2006

Proteasome inhibitors uncouple rhesus TRIM5alpha restriction of HIV-1 reverse transcription and infection.

The primate TRIM5alpha proteins have recently been defined as cellular restriction factors, preventing primate infection by retroviruses from different species. For instance, rhesus TRIM5alpha (rhTRIM5alpha) restricts infection by HIV-1. Virtually all TRIM5alpha proteins block the early replication of retroviruses by preventing the accumulation of reverse transcription products, but the underlying mechanism remains unclear. In this article, we find that disrupting proteasome function alters rhTRIM5alpha localization and allows the normal generation of HIV-1 late reverse transcription products, even though HIV-1 infection and the generation of nuclear 1-LTR and 2-LTR viral cDNA forms remain impaired. This finding suggests rhTRIM5alpha restricts HIV infection in two distinct phases: (i) altering the normal passage of the reverse-transcribing viral genome to the nucleus and (ii) targeting the reverse transcription complex to be disrupted by the proteasome. Because proteasome inhibitor blocks the second phase, accumulation of a nonfunctional viral DNA genome can be readily observed. Defining each phase may reveal HIV-1 targets for future antiviral therapy in which dual blockade may be equally as effective as naturally occurring rhTRIM5alpha protein in preventing HIV-1 infection in vivo.

Animals↗

PubMed2006

Proteasome inhibition reveals that a functional preintegration complex intermediate can be generated during restriction by diverse TRIM5 proteins.

The primate TRIM5 proteins constitute a class of restriction factors that prevent host cell infection by retroviruses from different species. The TRIM5 proteins act early after virion entry and prevent viral reverse transcription products from accumulating. We recently found that proteasome inhibitors altered the rhesus monkey TRIM5alpha restriction of human immunodeficiency virus type 1 (HIV-1), allowing reverse transcription products to accumulate even though viral infection remained blocked. To assess whether sensitivity to proteasome inhibitors was a common feature of primate TRIM5 proteins, we conducted a similar analysis of restriction mediated by owl monkey TRIM-cyclophilin A (CypA) or human TRIM5alpha. Similar to rhesus monkey TRIM5alpha restriction, proteasome inhibition prevented owl monkey TRIM-CypA restriction of HIV-1 reverse transcription, even though HIV-1 infection and the output of 2-LTR circles remained impaired. Likewise, proteasome inhibition alleviated human TRIM5alpha restriction of N-tropic murine leukemia virus reverse transcription. Finally, HIV-1 reverse transcription products escaping rhesus TRIM5alpha restriction by proteasome inhibition were fully competent for integration in vitro, demonstrating that TRIM5alpha likely prevents the viral cDNA from accessing chromosomal target DNA. Collectively, these data indicate that the diverse TRIM5 proteins inhibit retroviral infection in multiple ways and that inhibition of reverse transcription products is not necessary for TRIM5-mediated restriction of retroviral infection.

Animals↗

PubMed2004

HIV accessory proteins and surviving the host cell.

Human immunodeficiency virus generates the accessory proteins Nef, viral infectivity factor (Vif), viral protein R, and viral protein U or viral protein X during viral replication in host cells. Although the significance of these accessory proteins is often lost in vitro, they are essential for viral pathogenesis in vivo. Therefore, these proteins have much potential as antiviral targets. Recent data reveal Vif perturbs an ill-defined antiviral pathway in host cells allowing HIV replication. These data highlight a common feature among HIV accessory proteins in manipulating the host to aid viral pathogenesis. Therefore, these new insights into Vif and other HIV accessory proteins are reviewed, emphasizing host cell interactions and new targets for therapeutic intervention.

HIV Infections↗

PubMed2004

Microbiologic findings in feedlot cattle with acute interstitial pneumonia.

OBJECTIVE: To test the hypothesis that feedlot cattle with acute interstitial pneumonia (AIP) have bacterial infection of the lung or liver and concurrent bovine respiratory syncytial virus (BRSV) infection significantly more often than pen mates without AIP ANIMALS: 39 feedlot cattle with signs consistent with AIP and no history of treatment with antimicrobials and 32 healthy control cattle from the same pens. PROCEDURES: Lung and liver specimens were obtained postmortem for bacterial or mycoplasmal culture and histologic examination; lung tissue was assessed for BRSV infection immunohistochemically. RESULTS: Among affected cattle, 26 had AIP confirmed histologically. Lung tissue from 11 cattle with AIP yielded microbial respiratory tract pathogens on culture; tissues from control animals yielded no microbial growth. In 4 cattle with AIP and 2 control animals, liver abscesses were detected; bacteria were isolated from abscessed tissue in 3 and 1 of those animals, respectively. Immunohistochemically, 9 cattle with AIP and no control animals were BRSV-positive. Histologically, 9 AIP-affected cattle had only acute alveolar damage with exudation, and the other 17 had acute exudation with type II pneumocyte hyperplasia. No lesions of AIP were detected in control animals. Only 4 AIP-affected cattle had bacterial infection of the lung with concurrent BRSV infection. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that microbial respiratory tract pathogens are more common in cattle with AIP than in healthy pen mates. Control of bacterial pneumonia late in the feeding period may reduce the incidence of AIP at feedlots where AIP is a problem.

Animals↗