8 HIV-AIDS Cause Studies: Low Body O2

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J Biol Chem. 2009 Apr 24;284(17):11364-73. Epub 2009 Feb 9. Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1alpha expression. Deshmane SL, Mukerjee R, Fan S, Del Valle L, Michiels C, Sweet T, Rom I, Khalili K, Rappaport J, Amini S, Sawaya BE. Department of Neuroscience and Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122, USA. The detection of biomarkers of oxidative stress in brain tissue and cerebrospinal fluid of patients with human immunodeficiency virus, type 1 (HIV)-associated dementia indicates the involvement of stress pathways in the neuropathogenesis of AIDS. Although the biological importance of oxidative stress on events involved in AIDS neuropathogenesis and the HIV-1 proteins responsible for oxidative stress remain to be elucidated, our results point to the activation of hypoxia-inducible factor 1 (HIF-1) upon HIV-1 infection and its elevation in brain cells of AIDS patients with dementia. HIF-1 is a transcription factor that is responsive to oxygen. Under hypoxic conditions, HIF-1alpha becomes stable and translocates to the nucleus where it dimerizes with aryl hydrocarbon receptor nuclear translocator and modulates gene transcription. Activation of HIF-1 can also be mediated by the HIV-1 accessory protein Vpr. In addition, cellular components, including reactive oxygen species, contribute to the induction of HIF-1alpha. Our results show that Vpr induces reactive oxygen species by increasing H(2)O(2) production, which can contribute to HIF-1alpha accumulation. Interestingly, increased levels of HIF-1alpha stimulated HIV-1 gene transcription through HIF-1 association with HIV-1 long terminal repeat. These observations point to the existence of a positive feedback interplay between HIF-1alpha and Vpr and that, by inducing oxidative stress via activation of HIF-1, Vpr can induce HIV-1 gene expression and dysregulate multiple host cellular pathways.

Virchows Arch. 2009 Aug;455(2):159-70. Epub 2009 May 30. LANA-1, Bcl-2, Mcl-1 and HIF-1alpha protein expression in HIV-associated Kaposi sarcoma. Long E, Ilie M, Hofman V, Havet K, Selva E, Butori C, Lacour JP, Nelson AM, Cathomas G, Hofman P. Laboratory of Clinical and Experimental Pathology, Louis Pasteur Hospital, Nice 06002, France. Human herpesvirus 8 (HHV8) is necessary for Kaposi sarcoma (KS) to develop, but whether the tissue viral load is a marker of KS progression is still unclear. Little is known about the level of expression of apoptosis-regulating proteins and of hypoxia-inducible factors (HIFs) in KS tumour cells relative to HHV8 expression. We therefore investigated the expression of the latency-associated nuclear antigen (LANA-1) of HHV8, Bcl-2, Mcl-1, Bax, Bcl-xL, caspase 3 and HIF-1alphain KS tissue specimens at different stages of the disease. The expression of these proteins was evaluated immunohistochemically using tissue microarrays (TMAs) in tissue specimens from 245 HIV-positive patients at different stages of the disease. Both LANA-1 and HIF-1alpha were expressed in KS biopsies taken at different stages, but their level increased throughout tumour progression. Additionally, the levels of Bcl-2 and Mcl-1 were higher in visceral KS lesions compared to levels observed in cutaneous and mucosal KS. This study demonstrates that late tumour stages of KS in tissues from HIV-positive patients are associated with high levels of LANA-1, HIF-1alpha and of the anti-apoptotic proteins, Bcl-2 and Mcl-1. Finally, the expression of these proteins can be potentially used as a tissue biomarker in defining patients with a higher risk of disease progression.

Wien Klin Wochenschr. 2005;117 Suppl 4:49-55. Clinical features, aetiology and short-term outcome of interstitial pneumonitis in HIV/AIDS patients at Bamrasnaradura Hospital, Nonthaburi, Thailand. Knauer A, Das AK, Tansuphasawadikul S, Supanaranond W, Pitisuttithum P, Wernsdorfer WH. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. This prospective study was conducted at Bamrasnaradura Hospital from November 11, 2002, until January 5, 2003, in order to describe the clinical manifestations and determine the aetiologies as well as to assess the short-term outcome of interstitial pneumonitis in HIV/AIDS patients. 59 patients with interstitial infiltrates on chest radiographs were included in the study. Tuberculosis (TB) was the most common diagnosis (44%), followed by Pneumocystis pneumonia (PCP) (25.4%), bacterial pneumonia (20.3%) and fungal pneumonia (10.2%). In TB, compared to other diagnoses, a mild cough (p = 0.031), pallor (p = 0.021), lymphadenopathy (p < 0.001), an absence of skin lesions (p = 0.003), a higher mean body temperature (p = 0.004) and an absence of dyspnoea on exertion (p = 0.042) were significant findings. In PCP, compared to other diagnoses, dyspnoea on exertion (p = 0.014), nonpurulent sputum production (p = 0.047), a higher mean respiratory rate (p < 0.001), and an absence of lymphadenopathy (p < 0.001) were significant factors. In bacterial pneumonia, compared to other diagnoses, production of purulent sputum (p = 0.014), haemoptysis (p = 0.006), skin lesions (p = 0.002) and severe cough (p = 0.040) were significantly associated factors. In fungal pneumonia, compared to other diagnoses, headache and papulonecrotic skin lesions were common findings, but no factor showed a significant association. After four weeks, 59.3% patients were alive and 13.6% had died. Among those alive, 88.6% had clinically improved. The cumulative survival after 28 days was highest among PCP patients, followed by bacterial pneumonia, TB and fungal pneumonia, but these differences were statistically not significant (p = 0.453).

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2004 May;16(5):284-6. [Study of infusion of oxygen-enriched liquid to correct severe hypoxemia in infectious diseases: a report of pilot clinical study] [Article in Chinese] He Q, Xu C, Wang S, Cui JJ, Duan G, Ye TS, Yang DG, Zhou BP, Zhao LS. Donghu Hospital of Shenzhen, Shenzhen 518020, Guangdong, China. OBJECTIVE: To investigate a new therapy for effectively correcting severe hypoxemia in patients with infectious diseases by infusion of oxygen-enriched liquid, in order to raise the partial pressure of blood oxygen without passing through pathologically damaged alveoli of such patients. METHODS: Intravenous drip with oxygen-enriched liquids was given to 6 cases suffering from severe acute respiratory syndrome (SARS), and 3 cases of acquired immune deficiency syndrome (AIDS) in the course of treatment for 1 to 5 days, 500-700 ml per day. RESULTS: For all the 9 SARS cases, their hypoxemia was gradually corrected to normal in 20 minutes’ or 4 hours’ intravenous drip with oxygen-enriched liquid. Respiratory rate decreased from 29-49 breath/min to 18-22 breath/min, heart rate decreased from 89-145 beats/min to 60-79 beats/min, two faint patients regained consciousness, hypoxemia was redressed, partial pressure of oxygen in artery increased from 56 mm Hg (1 mm Hg=0.133 kPa) to 87 mm Hg, saturation of oxygen increased from 0.89 to 0.96. CONCLUSION: Intravenous drip of the oxygen-enriched liquid effectively helped correct the hypoxemia of SARS and other infectious diseases cases by bypassing the diseased alveoli through which oxygen would not pass into the blood by conventional oxygen inhalation. This therapy of oxygen-enriched liquid infusion could be quite life-saving in the combined treatment for SARS and other infectious diseases.

Med Hypotheses. 2002 Jun;58(6):439-43. Human-bacteria nitric oxide cycles in HIV-1 infection. Zhang H, Boring D, Haverkos H. Food and Drug Administration, Center for Drug Evaluation and Research, Division of Antiviral Drug Products, Rockville, USA. …In HIV infection, however, the NO(3)(-) is converted into NO and nitrite NO(2)(-) and recirculated in the body, perhaps as a result of concomitant opportunistic bacterial infections and cellular hypoxia…

Ann N Y Acad Sci. 2001 Nov;946:82-94. Pathogenesis of HIV-related pulmonary hypertension. Pellicelli AM, Palmieri F, Cicalini S, Petrosillo N. Istituto Nazionale per le Malattie Infettive, Lazzaro Spallanzani, IRCCS, Rome, Italy. …Chronic hypoxia is observed with increased frequency in HIV patients…

Indian J Pediatr. 1999 Nov-Dec;66(6):895-904. Pulmonary manifestations of pediatric HIV infection. Khare MD, Sharland M. Pediatric Infectious Diseases Unit, St. George’s Hospital, London, United Kingdom. Vertically acquired HIV infection is becoming increasingly common in India. The main clinical manifestations of HIV in childhood are growth failure, lymphadenopathy, chronic cough and fever, recurrent pulmonary infections, and persistent diarrhea… The commonest AIDS diagnosis in infancy is PCP, presenting in infancy with tachypnea, hypoxia, and bilateral opacification on chest-X-ray (CXR)…

J Med Assoc Thai. 1996 Aug;79(8):477-85. Pulmonary infections in HIV infected patients. Mootsikapun P, Chetchotisakd P, Intarapoka B. Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand. We retrospectively reviewed causes, clinical presentations and chest radiographs of pulmonary infections in symptomatic HIV infected patients diagnosed in Srinagarind Hospital from February 1992 to 1994. We found 95 episodes of pulmonary infections in 88 HIV infected patients enrolled in our review. The three most common pathogens were Mycobacterium tuberculosis (37.2%), Pneumocystis carinii (23.8%), and Cryptococcus (15.2%). Coexistent pulmonary infections were seen in 10.5 per cent, mostly due to P. carinii and Cryptococcus neoformans. Extrapulmonary infections were also common, particularly with M. tuberculosis (49%) and C. neoformans (100%). The common clinical presentations were fever, dyspnea, and cough which frequency varied among the organisms. Chest radiographs were nonspecific, the most common finding was bilateral pulmonary infiltrates except that bacterial pneumonia usually presented with unilateral infiltrates. All patients wit PC had significant hypoxia (PaO2 < 70 mmHg)

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