scholarly journals SIV/SHIV-Zika coinfection does not alter disease pathogenesis in adult non-pregnant Rhesus Macaques

2018 ◽  
Author(s):  
Mehdi R. M. Bidokhti ◽  
Debashis Dutta ◽  
Lepakshe S. V. Madduri ◽  
Shawna M. Woollard ◽  
Robert Norgren ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Epidemiological Studies ◽  
Disease Pathogenesis ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Tropical Infectious Diseases

AbstractDue to the large geographical overlap of populations exposed to Zika virus (ZIKV) and human immunodeficiency virus (HIV), understanding disease pathogenesis in such coinfections is urgently needed. We used chronically infected simian immunodeficiency virus and chimeric simian human immunodeficiency virus (SIV/SHIV) macaques and inoculated with ZIKV. Plasma viral loads of both SIV/SHIV and ZIKV showed no significant changes as compared to ZIKV alone-infected animals. Tissue clearance of ZIKV was observed similarly. Furthermore, minimal changes in cytokines/chemokines were observed. Collectively, these data suggest that coinfection may not alter disease pathogenesis and warrants large HIV-ZIKV epidemiological studies to validate these findings.Author SummaryThe co-infection incidence of human immunodeficiency virus (HIV) infection and neglected tropical infectious diseases is increasing due to the large geographical overlap of populations exposed to both of these viruses. Thus, researching on such coinfection is of particular importance. In this study, we investigated HIV-ZIKV coinfection dynamics in adult non-pregnant Rhesus Macaques model chronically infected with simian immunodeficiency virus (SIV) - or chimeric simian human immunodeficiency virus (SHIV). We found that post ZIKV inoculation, plasma viral loads were similar to ZIKV alone infected animals in addition to minimal changes of cytokines. Dynamics of SIV and SHIV also did not change. Tissue clearance of ZIKV was found 67 months later. Our findings provide insights into HIV-ZKIV coinfection to determine the alteration of their pathogenesis.

scholarly journals Control of Simian Immunodeficiency Virus SIVmac239 Is Not Predicted by Inheritance of Mamu-B*17-Containing Haplotypes

2006 ◽  
Vol 81 (1) ◽  
pp. 406-410 ◽  
Author(s):  
Jason A. Wojcechowskyj ◽  
Levi J. Yant ◽  
Roger W. Wiseman ◽  
Shelby L. O'Connor ◽  
David H. O'Connor
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Virus Disease ◽  
Rhesus Macaques ◽  
Host Genetics ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
Identical By Descent ◽  
Immunodeficiency Virus

ABSTRACT It is well established that host genetics, especially major histocompatibility complex (MHC) genes, are important determinants of human immunodeficiency virus disease progression. Studies with simian immunodeficiency virus (SIV)-infected Indian rhesus macaques have associated Mamu-B*17 with control of virus replication. Using microsatellite haplotyping of the 5-Mb MHC region, we compared disease progression among SIVmac239-infected Indian rhesus macaques that possess Mamu-B*17-containing MHC haplotypes that are identical by descent. We discovered that SIV-infected animals possessing identical Mamu-B*17-containing haplotypes had widely divergent disease courses. Our results demonstrate that the inheritance of a particular Mamu-B*17-containing haplotype is not sufficient to predict SIV disease outcome.

scholarly journals With Minimal Systemic T-Cell Expansion, CD8+ T Cells Mediate Protection of Rhesus Macaques Immunized with Attenuated Simian-Human Immunodeficiency Virus SHIV89.6 from Vaginal Challenge with Simian Immunodeficiency Virus

2008 ◽  
Vol 82 (22) ◽  
pp. 11181-11196 ◽  
Author(s):  
Meritxell Genescà ◽  
Pamela J. Skinner ◽  
Jung Joo Hong ◽  
Jun Li ◽  
Ding Lu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
T Cell Response ◽  
Lymphoid Tissues ◽  
Vaginal Mucosa ◽  
Challenge Virus ◽  
Immunodeficiency Virus

ABSTRACT The presence, at the time of challenge, of antiviral effector T cells in the vaginal mucosa of female rhesus macaques immunized with live-attenuated simian-human immunodeficiency virus 89.6 (SHIV89.6) is associated with consistent and reproducible protection from pathogenic simian immunodeficiency virus (SIV) vaginal challenge (18). Here, we definitively demonstrate the protective role of the SIV-specific CD8+ T-cell response in SHIV-immunized monkeys by CD8+ lymphocyte depletion, an intervention that abrogated SHIV-mediated control of challenge virus replication and largely eliminated the SIV-specific T-cell responses in blood, lymph nodes, and genital mucosa. While in the T-cell-intact SHIV-immunized animals, polyfunctional and degranulating SIV-specific CD8+ T cells were present in the genital tract and lymphoid tissues from the day of challenge until day 14 postchallenge, strikingly, expansion of SIV-specific CD8+ T cells in the immunized monkeys was minimal and limited to the vagina. Thus, protection from uncontrolled SIV replication in animals immunized with attenuated SHIV89.6 is primarily mediated by CD8+ T cells that do not undergo dramatic systemic expansion after SIV challenge. These findings demonstrate that despite, and perhaps because of, minimal systemic expansion of T cells at the time of challenge, a stable population of effector-cytotoxic CD8+ T cells can provide significant protection from vaginal SIV challenge.

scholarly journals Efavirenz Therapy in Rhesus Macaques Infected with a Chimera of Simian Immunodeficiency Virus Containing Reverse Transcriptase from Human Immunodeficiency Virus Type 1

2004 ◽  
Vol 48 (9) ◽  
pp. 3483-3490 ◽  
Author(s):  
Michael J. Hofman ◽  
Joanne Higgins ◽  
Timothy B. Matthews ◽  
Niels C. Pedersen ◽  
Chalet Tan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Simian Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Rhesus Macaques ◽  
Immunodeficiency Virus ◽  
Resistant Mutants ◽  
Hiv 1

ABSTRACT The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9 ± 4.5 nM, and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility. The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week. The virus load rebounded within 3 weeks in one treated animal and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations. The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz.

scholarly journals Immunization of Newborn Rhesus Macaques with Simian Immunodeficiency Virus (SIV) Vaccines Prolongs Survival after Oral Challenge with Virulent SIVmac251

2003 ◽  
Vol 77 (1) ◽  
pp. 179-190 ◽  
Author(s):  
Koen K. A. Van Rompay ◽  
Jennifer L. Greenier ◽  
Kelly Stefano Cole ◽  
Patricia Earl ◽  
Bernard Moss ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Disease Free Survival ◽  
Active Immunization ◽  
Pediatric Hiv ◽  
Maternal Antibodies ◽  
Immunization Strategies ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus

ABSTRACT There is an urgent need for active immunization strategies that, if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (HIV) infection through breast-feeding. Better knowledge of the immunogenic properties of vaccine candidates in infants and of the effect of maternal antibodies on vaccine efficacy will aid in the development of such a neonatal HIV vaccine. Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model of pediatric HIV infection with which to address these questions. Groups of infant macaques were immunized at birth and 3 weeks of age with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol, and Env (MVA-SIVgpe) or live-attenuated SIVmac1A11. One MVA-SIVgpe-immunized group had maternally derived anti-SIV antibodies prior to immunization. Animals were challenged orally at 4 weeks of age with a genetically heterogeneous stock of virulent SIVmac251. Although all animals became infected, the immunized animals mounted better antiviral antibody responses, controlled virus levels more effectively, and had a longer disease-free survival than the unvaccinated infected monkeys. Maternal antibodies did not significantly reduce the efficacy of the MVA-SIVgpe vaccine. In conclusion, although the tested vaccines delayed the onset of AIDS, further studies are warranted to determine whether a vaccine that elicits stronger early immune responses at the time of virus exposure may be able to prevent viral infection or AIDS in infants.

scholarly journals Use of a Small Molecule CCR5 Inhibitor in Macaques to Treat Simian Immunodeficiency Virus Infection or Prevent Simian–Human Immunodeficiency Virus Infection

2003 ◽  
Vol 198 (10) ◽  
pp. 1551-1562 ◽  
Author(s):  
Ronald S. Veazey ◽  
Per Johan Klasse ◽  
Thomas J. Ketas ◽  
Jacqueline D. Reeves ◽  
Michael Piatak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Small Molecule ◽  
Rhesus Macaques ◽  
Sexual Transmission ◽  
Immunodeficiency Virus ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) fuses with cells after sequential interactions between its envelope glycoproteins, CD4 and a coreceptor, usually CC chemokine receptor 5 (CCR5) or CXC receptor 4 (CXCR4). CMPD 167 is a CCR5-specific small molecule with potent antiviral activity in vitro. We show that CMPD 167 caused a rapid and substantial (4–200-fold) decrease in plasma viremia in six rhesus macaques chronically infected with simian immunodeficiency virus (SIV) strains SIVmac251 or SIVB670, but not in an animal infected with the X4 simian–human immunodeficiency virus (SHIV), SHIV-89.6P. In three of the SIV-infected animals, viremia reduction was sustained. In one, there was a rapid, but partial, rebound and in another, there was a rapid and complete rebound. There was a substantial delay (>21 d) between the end of therapy and the onset of full viremia rebound in two animals. We also evaluated whether vaginal administration of gel-formulated CMPD 167 could prevent vaginal transmission of the R5 virus, SHIV-162P4. Complete protection occurred in only 2 of 11 animals, but early viral replication was significantly less in the 11 CMPD 167-recipients than in 9 controls receiving carrier gel. These findings support the development of small molecule CCR5 inhibitors as antiviral therapies, and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission.

scholarly journals Genetic Analysis of Simian Immunodeficiency Virus Expressed in Milk and Selectively Transmitted through Breastfeeding

2006 ◽  
Vol 80 (8) ◽  
pp. 3721-3731 ◽  
Author(s):  
Jenna Rychert ◽  
Nedra Lacour ◽  
Angela Martin Amedee
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Negative Charge ◽  
Rhesus Macaques ◽  
Chronic Phase ◽  
Disease Course ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Single Genotype ◽  
Efficient Expression ◽  
Maternal Disease

ABSTRACT To develop effective intervention strategies that prevent breast milk transmission of human immunodeficiency virus (HIV), we must understand the specific viral properties and mechanisms responsible for infant infection. We have used lactating rhesus macaques infected with a pathogenic simian immunodeficiency virus (SIV) stock to analyze the viral genotypes expressed in plasma and milk throughout the disease course and to identify those variants ultimately transmitted to infants through breastfeeding. In these studies we observed mother-to-infant transmission of SIV/DeltaB670 by eight females during the chronic phase of disease, and we analyzed by heteroduplex tracking assays and sequence analysis the distribution and fluctuations in viral genotypes expressed. Each female expressed multiple V1 envelope genotypes in milk near the time of transmission, while a single genotype was found in each of the infants. Variants transmitted to infants were not expressed throughout the maternal disease course but were only detected near the time of transmission. The emergence of the transmitted genotype in the dam typically occurred in plasma before milk and was coincident with increased milk viral loads. Transmitted genotypes tended to be longer and more glycosylated and had a less negative charge over the V1 region compared to viral genotypes expressed in milk but not transmitted. These observations demonstrate that specific viral genotypes are selectively transmitted to infants through breastfeeding and support the hypothesis that transmission occurs as genotypes adapt for efficient expression in milk.

scholarly journals Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian–human immunodeficiency virus infection in macaques

2012 ◽  
Vol 93 (7) ◽  
pp. 1506-1518 ◽  
Author(s):  
Gui-Bo Yang ◽  
Yufei Wang ◽  
Kaboutar Babaahmady ◽  
Jørgen Schøller ◽  
Durdana Rahman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Major Histocompatibility Complex ◽  
Rhesus Macaques ◽  
Class I ◽  
Major Histocompatibility ◽  
Viral Loads ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Peak Viral Load ◽  
Hiv Gp120

Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian–human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques. Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran. The vaccine was administered to two groups, each consisting of nine macaques, either subcutaneously (SC), or rectally and boosted by SC immunization. The controls were untreated or adjuvant-treated animals. Repetitive rectal challenges with up to ten doses of SHIV SF162.P4 showed a significant decrease in the peak and sequential viral RNA concentrations, and three macaques remained uninfected, in the nine SC-immunized animals, compared with infection in all nine controls. Macaques immunized rectally followed by SC boosters showed a less significant decrease in both sequential and peak viral loads compared with the SC-immunized animals, and all were infected following rectal challenge with SHIV SF162.P4. Plasma and mucosal IgG and IgA antibodies to Mamu class I alleles and HIV gp120, as well as to RANTES (regulated upon activation, normal T-cell expressed, and secreted; CCR5) were increased, and showed significant inverse correlations with the peak viral load. These results suggested that allo-immunization with recombinant MHC constructs linked to HIV–SIV antigens merits further investigation in preventing HIV-1 infection.

scholarly journals Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques

2016 ◽  
Vol 90 (10) ◽  
pp. 4981-4989 ◽  
Author(s):  
Tiffany Hensley-McBain ◽  
Alexander S. Zevin ◽  
Jennifer Manuzak ◽  
Elise Smith ◽  
Jillian Gile ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Antibiotic Treatment ◽  
T Cell Activation ◽  
Rhesus Macaques ◽  
Bacterial Community Composition ◽  
Intestinal Microbiome ◽  
Th22 Cells ◽  
Immunodeficiency Virus ◽  
Taxonomic Groups

ABSTRACTAn altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4+T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.IMPORTANCEDue to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4+T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.

Sign in / Sign up

Export Citation Format

Share Document