Erling Rud

Carleton University · Department of Health Sciences

HIV infection is characterized by a host response composed of adaptive and innate immunity that partially limits viral replication; however, it ultimately fails in eradicating the virus. To model host gene expression during acute HIV infection, we infected cynomolgus macaques with the SIV/HIV-1 chimeric virus, SHIV89.6P, and profiled gene expressio...

In order to develop a successful subunit vaccine against infection with the human immunodeficiency virus (HIV), protective immune effector functions must be identified. Until now, there has been only indirect evidence that HIV-specific cytotoxic T lymphocytes (CTLs) fulfill this role. Using the macaque simian immunodeficiency virus (SIV) model, the...

A vaccine against AIDS will probably have to protect against challenge both by viable virus-infected cells and by cell-free virus. Eight cynomolgus macaques infected with attenuated simian immunodeficiency virus (SIV) were challenged (four each) with cell-free and cell-associated SIV. All were protected, whereas eight controls were all infected aft...

Experimental evidence from the simian immunodeficiency virus (SIV) model of AIDS has shown that the nef gene is critical in the pathogenesis of AIDS. Consequently, nef is of considerable interest in both antiviral drug and vaccine development. Preliminary findings in two rhesus macaques indicated that a deletion of only 12 bp found in the overlappi...

The proviral genome of the 32H reisolate of simian immunodeficiency of macaques (SIVmac32H) has been cloned and sequenced. Including both long terminal repeats, it is 10277 base pairs in length and contains open reading frames for all known SIV genes (gag, pol, vif, vpx, vpr, tat, rev, env and nef). This is the first report of an infectious SIVmac...

Vaccines and immunization programs can play a key role in addressing the growing challenge of antimicrobial resistance (AMR). Amongst the high priority vaccines in development are several AMR pathogens, including: Clostridium difficile, Staphylococcus aureus, Streptococcus pneumoniae, Mycobacterium tuberculosis and Neisseria gonorrhoeae. There is e...

The brain is assumed to be a sterile organ in the absence of disease although the impact of immune disruption is uncertain in terms of brain microbial diversity or quantity. To investigate microbial diversity and quantity in the brain, the profile of infectious agents was examined in pathologically normal and abnormal brains from persons with HIV/A...

Network analyses of host gene expression in relation to bacterial quantity. The identified 75 host genes associated with bacterial quantity were subjected to network analyses generating a network (IPA score 21) emphasizing genes that participated principally in cell morphology, division and maintenance function, e.g. calreticulin, SLC12A, KLF1, net...

Primers pairs used to amplify 16 s rRNA. (DOCX)

Bacterial detection in ODC and HIV patients with or without confirmed HIV encephalitis. Brain specimens were immunolabeled with anti-peptidoglycan antibody. Peptidoglycan-positive bodies were morphologically consistent with bacteria and distributed throughout the tissue (Magnification, left column, 100X) in all patients (Magnification, right column...

Agarose gel electrophoresis and ethidium bromide staining of 16 s rRNA PCR products. (A) Optimization of primer pairs was conducted by testing compatible primer pairs in a colony PCR protocol using E. coli DH5α as template. All reagents and primer pairs were tested for purity in reaction where ultrapure water was used as a template. Representative...

Detection and identification of bacterial 16 s V8 rRNA in human brain from HIV and ODC groups. (A) 16 s V8 rRNA sequences detected in HIV patients relative to ODC patients’ brain specimens by real time RT-PCR and normalized to GAPDH (Mean +/− SD). (B) Phylogenetic analysis of 16 s rRNA V8 region sequences derived from all brain specimens. Clustal a...

Host genes correlated with bacterial sequence tag abundance. (DOCX)

Primers used to detect RNA or DNA viruses. (DOCX)

Primers used for semi-quantitative RT-PCR analysis of host transcript expression. (DOCX)

The MHC class I-A and -B genes of cynomolgus macaques are highly polymorphic. These genes encode proteins presenting peptides to CD8+ T cells to initiate adaptive immune response. Recombination events are one way the diversity of these alleles can be increased. Such events have been well characterized in humans, but have not been as well characteri...

We report here novel Mafa-A, -AG and -B alleles identified in two groups of cynomolgus macaques.

Attenuated simian immunodeficiency virus (SIV) induces potent protection against infection with wild‐type virus, but the mechanism of this immunity remains obscure. Allogeneic antibodies, which arise within animals as a result of SIV infection, might protect against challenge with exogenous SIV grown in allogeneic cells. To test this hypothesis, ei...

Attempts to evaluate the protective effect of live attenuated SIV vaccine strains have yielded variable results depending on the route of immunization, the level of attenuation, the level of divergence between the vaccine candidate and the challenge. The protective mechanisms induced by these vaccines are still not well understood. In an effort to...

Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), the focus of the vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based vaccine trials in macaques challenged with simian/human immunodeficiency virus SHIV-89.6P hav...

Cross-species transmission of simian foamy virus (SFV) to human beings from chimpanzees, baboons, and African green monkeys has been described. Although macaques are the non-human primate most often handled in research, human infection with SFV from macaques has not been reported. Two of 46 primate-facility workers tested positive for antibodies th...

New viral infections in humans usually result from viruses that have been transmitted from other species as zoonoses. For example, it is accepted widely that human immunodeficiency virus (HIV) is the result of the propagation and adaptation of a simian immunodeficiency virus (SIV) from nonhuman primates to man [1]. Previously, we reported productiv...

In this study, we investigated whether a type of retroviral interference might be one mechanism that mediates the powerful protection induced by live attenuated SIVC8. Our results show that retroviral interference could be demonstrated between SIV and SHIV-HXBc2 in human T-cell lines chronically infected with either SIVC8 or SIVJ5. Lymphocytes from...

We aimed to determine the prevalence of HIV infection and associated risk factors among Montrealers of Haitian origin. We carried out a voluntary, anonymous survey in 7 primary care medical clinics in Montreal among 5039 persons aged 15 to 49 years born in Haiti or with at least one parent born in Haiti. The participation rate was 94.3%. Overall, H...

HIV-1 viral load quantitation is now recognized as a useful tool to monitor the efficiency of antiviral treatment and a powerful predictor of disease outcome. Three HIV-1 viral load quantitation methods have been currently available as commercial kits in Canada since 1996. To evaluate the ability to quantify HIV-1 RNA in plasma of the Amplicor HIV...

To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2. Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm int...

The aim of this study was to evaluate the role of CTLs in the protection from challenge with pathogenic SHIV in macaques vaccinated with attenuated virus. More specifically, we have analyzed the CTL response in cynomolgus macaques vaccinated/infected with the attenuated SIVmacC8 or the wild-type SIVmacJ5 and correlated these responses to the protec...

Variants of simian immunodeficiency virus (SIV) that display greater than 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) were generated through in vitro passage and drug selection. The polymerase regions of several of these resistant viruses were sequenced and were found to share either of two codon alterations a...

Good protection against systemic challenge in the SIVmac model of AIDS has been provided by prior infection with attenuated virus. To determine if such protection extends to intrarectal mucosal challenge two molecular clones, SIVmacC8 and SIVmacJ5, were used in this study. SIVmacC8 has an attenuated phenotype in vivo, due to a 12-bp deletion in the...

Convincing data on experimental vaccines against AIDS have been obtained in the simian immunodeficiency virus (SIV) macaque model by preinfection with a virus attenuated by a nef deletion. To investigate the efficacy of a nef deletion mutant of SIVmac32H called pC8 as a live-attenuated vaccine after shorter preinfection periods and to learn more ab...

To date, some success has been achieved with several experimental vaccines against AIDS in the available animal models. In the simian immunodeficiency virus (SIV) macaque model protection against superinfection was obtained by preinfection with a virus attenuated by a deletion in nef. To investigate the efficacy of SIVmac32H(pC8), a nef deletion mu...

To gain further insight into the ability of subunit vaccines to protect monkeys from experimental infection with simian immunodeficiency virus (SIV), two groups of cynomolgus macaques were immunized with either recombinant SIVmac32H-derived envelope glycoproteins (Env) incorporated into immune-stimulating complexes (iscoms) (group A) or with these...

Prior infection with a nef-deleted simian immunodeficiency virus (SIV) protects macaques not only against a homologous pathogenic SIV challenge but also against challenge with a chimeric SIV expressing a human immunodeficiency virus type 1 env gene (SHIV). Since this SHIV is itself nonpathogenic, we sought to explore the use of a nonpathogenic SHIV...

The transmembrane proteins (TMP) of immunodeficiency lentiviruses are primary candidates for inclusion in AIDS vaccines, the design and testing of which is facilitated by the SIV-macaque infection model. Antibody responses to linear determinants in the SIVmac TMP were investigated in rhesus macaques either infected with the SIVmac J5 molecular clon...

A vaccine against AIDS will probably have to protect against challenge both by viable virus-infected cells and by cell-free virus. Eight cynomolgus macaques infected with attenuated simian immunodeficiency virus (SIV) were challenged (four each) with cell-free and cell-associated SIV. All were protected, whereas eight controls were all infected aft...

To characterize the serological response to SIV envelope, induced by vaccination with different envelope immunogens or by SIV infection, plasma samples from 11 cynomolgus macaques infected with simian immunodeficiency virus (SIV) and from 16 macaques vaccinated with three different recombinant envelope proteins were analyzed by (1) ELISA, using a v...

Two commercially available expression vectors were modified to generate plasmids pGEXcPk and pQ9cPk. Proteins expressed from pGEXcPk and pQ9cPk had a short oligopeptide tag termed Pk at their carboxy termini and either glutathione S-transferase (GST) or a small histidine (His) tag, respectively, at their N termini. GST fusion proteins can be purifi...

The envelope glycoprotein, gp160, of human (HIV) and simian (SIV) immunodeficiency viruses mediates virus-host cell binding followed by fusion of the viral and plasma membranes. The envelope proteins are known to exist as non-covalently associated oligomers on the virus surface. The production of permanent mammalian cell lines that constitutively s...

Forty-six overlapping peptides (20-mers) representing the amino acid sequence of the external envelope glycoprotein of simian immunodeficiency virus (SIVmac; 32H isolate) were used to investigate linear antigenic sites recognized by antibodies in sera from SIV-infected rhesus macaques and in animals vaccinated with formalin-inactivated SIV. The rea...

Macaques were immunised with lentil lectin purified recombinant SIVmac (BK28) derived gp160 (rgp160) with or without live vaccinia (vac)‐env (BK28) priming, followed by a final boost with solid matrix antibody antigen (SMAA)‐gp160 (J5) complexes and challenged with the SIVmac molecularly cloned virus J5M. Rgp160 and vac‐env plus gp160 induced stron...

Subunit approaches to vaccines against viral diseases have resulted in the development of a number of methods for presentation of defined epitopes to the immune system. We have exploited a highly immunogenic presentation system based on hepatitis B core antigen (HBcAg) particles to produce a number of candidate vaccines against simian immunodeficie...

Ten new monoclonal antibodies (MAbs) to SIV envelope were produced and characterized. Using a panel of 28 MAbs, 10 antibody binding sites on SIV envelope protein were identified. Seven sites were located in gp120 and three in gp41. Five sites in gp120 and two in gp41 were defined by overlapping peptides. The remaining two sites on gp120 and one on...

We have determined the nucleotide sequence of the L gene of vesicular stomatitis virus (VSV), New Jersey serotype (Ogden strain) by primer extension dideoxy sequencing of the genomic RNA with reverse transcriptase. This analysis completes the entire genomic sequence of the VSVNJ (Ogden). Comparison of the deduced amino acid sequence of this L prote...

The 5′-terminal sequence of VSVNJ (Ogden) and VSVNJ (Hazelhurst) was compared in an attempt to understand why the defective interfering particle, DI-LT, heterotypically interferes with VSVNJ (Ogden) but not with VSVNJ (Hazelhurst). The 5′-terminal sequence of VSVNJ (Ogden) genomic RNA was determined by direct RNA sequencing and by DNA sequencing of...

Defective interfering (DI) particles have been isolated from a heat-resistant strain of the New Jersey (Ogden) serotype of vesicular stomatitis virus (VSV). Most of these DI particles contain various portions of all five cistrons of VSV. The two largest DI particles, NJ-121 and NJ-PG2, represent approximately 60% of the standard virus genome and co...

The asterisk (*) indicating the transcriptional initiation site of the HPIV3 nucleoprotein (NP) mRNA was omitted from the sequence and should be above the U residue at nucleotide position number 56.

The genome of bunya viruses consists of three single-stranded, negative-sense, RNA molecules designated as L, M, and S. For snowshoe hare (SSH) virus, a member of the California encephalitis serogroup of bunyaviruses, it has been demonstrated by genetic, molecular, and DNA sequencing studies that the S RNA (3.3x10 daltons) codes for the structural...

Laboratory tests were conducted to evaluate the effect of simultaneous and sequential treatments of cytoplasmic or nuclear polyhedrosis viruses and a synthetic pyrethroid, permethrin (Ambush),on the larvae of Euxoa scandens (Riley). A significant increase in total mortality occurred when permethrin was applied to larvae previously infected for a pe...

The white cutworm, Euxoa scandens (Riley), is a sporadic pest of tobacco in Quebec (Mailloux and Desrosiers 1978), asparagus in Michigan (A. L. Wells, pers. comm.), and other vegetable crops grown in light sandy soils (Beirne 1971). The immature larvae overwinter and cause serious damage when they resume feeding in the spring (Hudson and Wood 1930)...